Tokushima University / Educator and Researcher Directory --- Morita, Akinori

Personal Web Page

https://www.tokushima-u.ac.jp/med/health_science/course/iyohoshasen/biomedical-science-technology/

https://researchmap.jp/read0135466 (researchmap)

Field of Study

○	Radiation Biology, Radiation Oncology, Molecular and Cellular Biology, Biochemistry, Chemical Biology

Subject of Study

○	Development of novel kind of radioprotectors that relieve the damage of normal tissues in radiation injury., Development of radioprotective agents and anti-inflammatory agents by controlling immunoinflammatory responses.

Book / Paper

Book:

1.	Akinori Morita : 医用放射線辞典第6版執筆者(放射線生物学), KYORITSU SHUPPAN.CO.,LTD, Feb. 2023.
2.	Akinori Morita, 坂野康昌, 末永光八 and 黒田昌宏 : Fundamentals of Radiological Technology, Radiation Biology, KYORITSU SHUPPAN.CO.,LTD, Mar. 2020.
3.	松本義久編, Akinori Morita and 他 : Radiation biology to learn from mechanism of the human body, MEDICAL VIEW CO., LTD., Feb. 2017.

Academic Paper (Judged Full Paper):

1.	Hidetoshi Satoh, Shintaroh Ochi, Kosuke Mizuno, Yutaka Saga, Shohei Ujita, Mihiro Toyoda, Yuichi Nishiyama, Kasumi Tada, Yosuke Matsushita, Yuichi Deguchi, Keiji Suzuki, Yoshimasa Tanaka, Hiroshi Ueda, Toshiya Inaba, Yoshio Hosoi, Akinori Morita and Shin Aoki : Design, synthesis and biological evaluation of 2-pyrrolone derivatives as radioprotectors., Bioorganic & Medicinal Chemistry, Vol.67, 2022. (Summary) It is known that p53 is an important transcription factor and plays a central role in ionizing radiation (IR)-induced DNA damage responses such as cell cycle arrest, DNA repair and apoptosis. We previously reported that regulating p53 protein is an effective strategy for modulating cell fate by reducing the acute side effects of radiation therapy. Herein, we report on the discovery of STK160830 as a new radioprotector from a chemical library at The University of Tokyo and the design, synthesis and biological evaluation of its derivatives. The radioprotective activity of STK160830 itself and its derivatives that were synthesized in this work was evaluated using a leukemia cell line, MOLT-4 cells as a model of normal cells that express the p53 protein in a structure-activity relationships (SAR) study. The experimental results suggest that a direct relationship exists between the inhibitory effect of these STK160830 derivatives on the expression level of p53 and their radioprotective activity and that the suppression of p53 by STK160830 derivatives contribute to protecting MOLT-4 cells from apoptosis that is induced by exposure to radiation. (Keyword) Apoptosis / DNA Damage / DNA Repair / Tumor Suppressor Protein p53 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2022.116764 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 35635928 ● Search Scopus @ Elsevier (PMID): 35635928 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2022.116764 (DOI: 10.1016/j.bmc.2022.116764, PubMed: 35635928)
2.	Akinori Morita, Shintaro Ochi, Hidetoshi Satoh, Shohei Ujita, Yosuke Matsushita, Kasumi Tada, Mihiro Toyoda, Yuichi Nishiyama, Kosuke Mizuno, Yuichi Deguchi, Keiji Suzuki, Yoshimasa Tanaka, Hiroshi Ueda, Toshiya Inaba, Yoshio Hosoi and Shin Aoki : A Novel RNA Synthesis Inhibitor, STK160830, Has Negligible DNA-Intercalating Activity for Triggering A p53 Response, and Can Inhibit p53-Dependent Apoptosis., Life, Vol.11, No.10, 2021. (Summary) RNA synthesis inhibitors and protein synthesis inhibitors are useful for investigating whether biological events with unknown mechanisms require transcription or translation; however, the dependence of RNA synthesis has been difficult to verify because many RNA synthesis inhibitors cause adverse events that trigger a p53 response. In this study, we screened a library containing 9600 core compounds and obtained STK160830 that shows anti-apoptotic effects in irradiated wild-type-p53-bearing human T-cell leukemia MOLT-4 cells and murine thymocytes. In many of the p53-impaired cells and p53-knockdown cells tested, STK160830 did not show a remarkable anti-apoptotic effect, suggesting that the anti-apoptotic activity is p53-dependent. In the expression analysis of p53, p53-target gene products, and reference proteins by immunoblotting, STK160830 down-regulated the expression of many of the proteins examined, and the downregulation correlated strongly with its inhibitory effect on cell death. mRNA expression analyses by qPCR and nascent RNA capture kit revealed that STK160830 showed a decreased mRNA expression, which was similar to that induced by the RNA synthesis inhibitor actinomycin D but differed to some extent. Furthermore, unlike other RNA synthesis inhibitors such as actinomycin D, p53 accumulation by STK160830 alone was negligible, and a DNA melting-curve analysis showed very weak DNA-intercalating activity, indicating that STK160830 is a useful inhibitor for RNA synthesis without triggering p53-mediated damage responses. (Tokushima University Institutional Repository) ● Metadata: 116405 (Link to Publication Site) ● Publication site (DOI): 10.3390/life11101087 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34685458 ● Search Scopus @ Elsevier (PMID): 34685458 ● Search Scopus @ Elsevier (DOI): 10.3390/life11101087 (Tokushima University Institutional Repository: 116405, DOI: 10.3390/life11101087, PubMed: 34685458)
3.	Yuichi Nishiyama, Akinori Morita, Shogo Tatsuta, Misaki Kanamaru, Masahiro Sakaue, Kenta Ueda, Manami Shono, Rie Fujita, Bing Wang, Yoshio Hosoi, Shin Aoki and Takeshi Sugai : Isorhamnetin Promotes 53BP1 Recruitment through the Enhancement of ATM Phosphorylation and Protects Mice from Radiation Gastrointestinal Syndrome., Genes, Vol.12, No.10, 2021. (Summary) Flavonoids are a subclass of polyphenols which are attractive, due to possessing various physiological activities, including a radioprotective effect. Tumor suppressor p53 is a primary regulator in the radiation response and is involved in the pathogenesis of radiation injuries. In this study, we revealed that isorhamnetin inhibited radiation cell death, and investigated its action mechanism focusing on DNA damage response. Although isorhamnetin moderated p53 activity, it promoted phosphorylation of ataxia telangiectasia mutated (ATM) and enhanced 53BP1 recruitment in irradiated cells. The radioprotective effect of isorhamnetin was not observed in the presence of ATM inhibitor, indicating that its protective effect was dependent on ATM. Furthermore, isorhamnetin-treated mice survived gastrointestinal death caused by a lethal dose of abdominal irradiation. These findings suggested that isorhamnetin enhances the ATM-dependent DNA repair process, which is presumably associated with the suppressive effect against GI syndrome. (Tokushima University Institutional Repository) ● Metadata: 116406 (Link to Publication Site) ● Publication site (DOI): 10.3390/genes12101514 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34680909 ● Search Scopus @ Elsevier (PMID): 34680909 ● Search Scopus @ Elsevier (DOI): 10.3390/genes12101514 (Tokushima University Institutional Repository: 116406, DOI: 10.3390/genes12101514, PubMed: 34680909)
4.	Yuichi Nishiyama, Akinori Morita, Bing Wang, Takuma Sakai, Dwi Ramadhani, Kaoru Tanaka, Megumi Sasatani, Shintaro Ochi, Masahide Tominaga, Hitoshi Ikushima, Junji Ueno, Mitsuru Nenoi and Shin Aoki : Evaluation of sodium orthovanadate as a radioprotective agent under total-body irradiation and partial-body irradiation conditions in mice., International Journal of Radiation Biology, Vol.97, No.9, 1241-1251, 2021. (Tokushima University Institutional Repository) ● Metadata: 116409 (Link to Publication Site) ● Publication site (DOI): 10.1080/09553002.2021.1941377 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34125648 ● Search Scopus @ Elsevier (PMID): 34125648 ● Search Scopus @ Elsevier (DOI): 10.1080/09553002.2021.1941377 (Tokushima University Institutional Repository: 116409, DOI: 10.1080/09553002.2021.1941377, PubMed: 34125648)
5.	Tomoka Yoda, Masateru Furuta, Tomohiko Tsutsumi, Seiki Ikeda, Shunsuke Yukizawa, Satoshi Arai, Akinori Morita, Kenji Yamatoya, Kazuya Nakata, Shusuke Tomoshige, Kenji Ohgane, Yuuki Furuyama, Kengo Sakaguchi, Fumio Sugawara, Susumu Kobayashi, Masahiko Ikekita and Kouji Kuramochi : Epo-C12 inhibits peroxiredoxin 1 peroxidase activity., Bioorganic & Medicinal Chemistry, Vol.41, 2021. (Summary) in Prx 1. The present study revealed that Prx 1 is one of the target proteins through which Epo-C12 exerts an apoptotic effect in BALL-1 cells. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2021.116203 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 34015702 ● Search Scopus @ Elsevier (PMID): 34015702 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2021.116203 (DOI: 10.1016/j.bmc.2021.116203, PubMed: 34015702)
6.	Akinori Morita, Bing Wang, Kaoru Tanaka, Takanori Katsube, Masahiro Murakami, Takashi Shimokawa, Yuichi Nishiyama, Shintaro Ochi, Hidetoshi Satoh, Mitsuru Nenoi and Shin Aoki : Protective Effects of p53 Regulatory Agents Against High-LET Radiation-Induced Injury in Mice., Frontiers in Public Health, Vol.8, 2020. (Summary) < 0.02), but not iron-ion irradiation, suggesting the moderate relief of the intestinal damage. These results demonstrated the effectiveness of p53 regulators on acute radiation syndrome induced by high-LET radiation. (Tokushima University Institutional Repository) ● Metadata: 115457 (Link to Publication Site) ● Publication site (DOI): 10.3389/fpubh.2020.601124 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 33344403 ● Summary page in Scopus @ Elsevier: 2-s2.0-85098120572 (Tokushima University Institutional Repository: 115457, DOI: 10.3389/fpubh.2020.601124, PubMed: 33344403, Elsevier: Scopus)
7.	Hironori Tanaka, Koichi Okamoto, Yasushi Sato, Takahiro Tanaka, Tetsu Tomonari, Fumika Nakamura, Yasuteru Fujino, Yasuhiro Mitsui, Hiroshi Miyamoto, Naoki Muguruma, Akinori Morita, Hitoshi Ikushima and Tetsuji Takayama : Synergistic anti-tumor activity of miriplatin and radiation through PUMA-mediated apoptosis in hepatocellular carcinoma., Journal of Gastroenterology, Vol.55, No.11, 1072-1086, 2020. (Summary) The prognosis for patients with unresectable advanced hepatocellular carcinoma (HCC) is poor. Miriplatin is a hydrophobic platinum compound that has a long retention time in lesions after transarterial chemoembolization (TACE). We investigated anti-tumor activity of miriplatin combined with irradiation on HCC cells, and its underlying mechanism of apoptosis. We also analyzed the effectiveness of miriplatin-TACE and radiotherapy for locally advanced HCC. Human HCC cell lines HepG2 and HuH-7 were treated with DPC (active form of miriplatin) and radiation, and synergy was evaluated using a combination index (CI). Apoptosis-related proteins and cell cycles were analyzed by western blotting and flowcytometry. We retrospectively analyzed treatment outcomes in 10 unresectable HCC patients with vascular/bile duct invasion treated with miriplatin-TACE and radiotherapy. DPC or X-ray irradiation decreased cell viability dose-dependently. DPC plus irradiation decreased cell viability synergistically in both cell lines (CI < 1, respectively). Cleaved PARP expression was induced much more strongly by DPC plus irradiation than by each treatment alone. Expression of p53 up-regulated modulator of apoptosis (PUMA) was significantly induced by the combination, and knockdown of PUMA with siRNA significantly decreased apoptosis in both cell lines. DPC plus irradiation caused sub-G1, G2/M, and S phase cell arrest in those cells. The combination of miriplatin-TACE and radiotherapy showed a high response rate for patients with locally advanced HCC despite small number of patients. Miriplatin plus irradiation had synergistic anti-tumor activity on HCC cells through PUMA-mediated apoptosis and cell cycle arrest. This combination may possibly be effective in treating locally advanced HCC. (Tokushima University Institutional Repository) ● Metadata: 115325 (Link to Publication Site) ● Publication site (DOI): 10.1007/s00535-020-01705-8 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 32666201 ● Summary page in Scopus @ Elsevier: 2-s2.0-85087895196 (Tokushima University Institutional Repository: 115325, DOI: 10.1007/s00535-020-01705-8, PubMed: 32666201, Elsevier: Scopus)
8.	Akinori Morita, Ippei Takahashi, Megumi Sasatani, Shin Aoki, Bing Wang, Shinya Ariyasu, Kaoru Tanaka, Tetsuji Yamaguchi, Akiko Sawa, Yurie Nishi, Tatsuro Teraoka, Shohei Ujita, Yosuke Kawate, Chihiro Yanagawa, Keiji Tanimoto, Atsushi Enomoto, Mitsuru Nenoi, Kenji Kamiya, Yasushi Nagata, Yoshio Hosoi and Toshiya Inaba : A chemical modulator of p53 transactivation that acts as a radioprotective agonist., Molecular Cancer Therapeutics, Vol.17, No.2, 432-442, 2017. (Summary) Inhibiting p53-dependent apoptosis by inhibitors of p53 is an effective strategy for preventing radiation-induced damage in hematopoietic lineages, while p53 and p21 also play radioprotective roles in the gastrointestinal epithelium. We previously identified some zinc(II) chelators, including 8-quinolinol derivatives that suppress apoptosis in attempts to discover compounds that target the zinc-binding site in p53. We found that 5-chloro-8-quinolinol (5CHQ) has a unique p53-modulating activity that shifts its transactivation from proapoptotic to protective responses including enhancing p21 induction and suppressing PUMA induction. This p53-modulating activity also influenced p53 and p53-target gene expression in unirradiated cells without inducing DNA damage. The specificity of 5CHQ for p53 and p21 was demonstrated by silencing the expression of each protein. These effects seems to be attributable to the sequence-specific alteration of p53 DNA-binding, as evaluated by chromatin immunoprecipitation and electrophoretic mobility shift assays. In addition, 5-chloro-8-methoxyquinoline itself had no antiapoptotic activity, indicating that the hydroxyl group at the 8-position is required for its antiapoptotic activity. We applied this remarkable agonistic activity to protecting the hematopoietic and gastrointestinal system in mouse irradiation models. The dose-reduction factors of 5CHQ in total-body and abdominally irradiated mice were about 1.2 and 1.3, respectively. 5CHQ effectively protected mouse epithelial stem cells from a lethal dose of abdominal irradiation. Furthermore, the specificity of 5CHQ for p53 in reducing the lethality induced by abdominal irradiation was revealed in Trp53-KO mice. These results indicate that the pharmacological upregulation of radioprotective p53-target genes is an effective strategy for addressing the gastrointestinal syndrome. (Tokushima University Institutional Repository) ● Metadata: 111999 (Link to Publication Site) ● Publication site (DOI): 10.1158/1535-7163.MCT-16-0554 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28939557 ● Summary page in Scopus @ Elsevier: 2-s2.0-85041474121 (Tokushima University Institutional Repository: 111999, DOI: 10.1158/1535-7163.MCT-16-0554, PubMed: 28939557, Elsevier: Scopus)
9.	Yukihiro Furusawa, Yuka Yamanouchi, Takashi Iizumi, Qing-Li Zhao, Yohei Mitsuhashi, Akinori Morita, Atushi Enomoto, Yoshiaki Tabuchi and Takashi Kondo : Checkpoint kinase 2 is dispensable for regulation of the p53 response but is required for G2/M arrest and cell survival in cells with p53 defects under heat stress., Apoptosis, 2017. (Summary) Hyperthermia induced by heat stress (HS) is known to inhibit proliferation and induce cell death in cancer. We previously demonstrated that checkpoint kinase 1 (Chk1) contributes to G2/M arrest and cell survival under HS; however, the role of Chk2, a functional analog of Chk1, in regulation of the cell cycle and cell death under HS is still unknown. Here, we addressed the role of Chk2 using Molt-4 cells with p53-targeted shRNA (Molt-4/shp53) and parental control cells (Molt-4/V). Chk2 inhibition suppressed C-terminal acetylation of p53 and delayed the induction of p53-target genes in Molt-4/V cells under HS; however, Chk2 inhibition failed to inhibit apoptosis induced by HS, indicating that Chk2 was dispensable for p53-dependent apoptosis under HS. In contrast, Chk2 inhibition abrogated G2/M arrest and promoted cell death induced by HS in HeLa cells and Molt-4/shp53 cells. Thus, we demonstrated for the first time that Chk2 was required for cell cycle arrest and cell survival, particularly in cells with p53 defects under HS. These findings indicated that Chk2 may be a selective target for p53-mutated or -deficient cancer treated with hyperthermia. (Link to Publication Site) ● Publication site (DOI): 10.1007/s10495-017-1402-2 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28733865 ● Search Scopus @ Elsevier (PMID): 28733865 ● Search Scopus @ Elsevier (DOI): 10.1007/s10495-017-1402-2 (DOI: 10.1007/s10495-017-1402-2, PubMed: 28733865)
10.	Atsushi Enomoto, Junko Yamada, Akinori Morita and Kiyoshi Miyagawa : Bisdemethoxycurcumin enhances X-ray-induced apoptosis possibly through p53/Bcl-2 pathway., Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol.815, 1-5, 2017. (Summary) Bisdemethoxycurcumin (BDMC), which is isolated from the rhizomes of Curcuma longa, has anti-inflammatory and anti-carcinogenic activities. Here we found that BDMC enhanced X-ray-induced apoptosis in human T-cell leukemia MOLT-4 cells. Knockdown of p53 significantly attenuated the radiosensitizing effect of BDMC. However, BDMC did not enhance X-ray-mediated activation of the p53 signaling pathway via p53's transactivation or mitochondrial translocation. On the other hand, BDMC promoted the X-ray-induced dephosphorylation at Ser 70 in Bcl-2's flexible loop regulatory domain and Bcl-2 binding to p53. Overexpressing Bcl-2 completely blocked the BDMC's radiosensitization effect. Our results indicate that BDMC stimulates the dephosphorylation and p53-binding activity of Bcl-2 and suggest that BDMC may induce a neutralization of Bcl-2's anti-apoptotic function, thereby enhancing X-ray-induced apoptosis. (Keyword) Apoptosis / Cell Line, Tumor / Curcumin / Humans / Proto-Oncogene Proteins c-bcl-2 / Tumor Suppressor Protein p53 / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1016/j.mrgentox.2016.12.005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28283087 ● Search Scopus @ Elsevier (PMID): 28283087 ● Search Scopus @ Elsevier (DOI): 10.1016/j.mrgentox.2016.12.005 (DOI: 10.1016/j.mrgentox.2016.12.005, PubMed: 28283087)
11.	Takanori Katsube, Bing Wang, Kaoru Tanaka, Yasuharu Ninomiya, Guillaume Varès, Taiki Kawagoshi, Naoko Shiomi, Yoshihisa Kubota, Qiang Liu, Akinori Morita, Tetsuo Nakajima and Mitsuru Nenoi : Effects of chronic restraint-induced stress on radiation-induced chromosomal aberrations in mouse splenocytes., Mutation Research/Genetic Toxicology and Environmental Mutagenesis, Vol.813, 18-26, 2016. (Summary) Both ionizing radiation (IR) and psychological stress (PS) cause detrimental effects on humans. A recent study showed that chronic restraint-induced PS (CRIPS) diminished the functions of Trp53 and enhanced radiocarcinogenesis in Trp53-heterozygous (Trp53(+/-)) mice. These findings had a marked impact on the academic field as well as the general public, particularly among residents living in areas radioactively contaminated by nuclear accidents. In an attempt to elucidate the modifying effects of CRIPS on radiation-induced health consequences in Trp53 wild-type (Trp53(+/+)) animals, investigations involving multidisciplinary analyses were performed. We herein demonstrated that CRIPS induced changes in the frequency of IR-induced chromosomal aberrations (CAs) in splenocytes. Five-week-old male Trp53(+/+) C57BL/6J mice were restrained for 6h per day for 28 consecutive days, and total body irradiation (TBI) at a dose of 4Gy was performed on the 8th day. Metaphase chromosome spreads prepared from splenocytes at the end of the 28-day restraint regimen were painted with fluorescence in situ hybridization (FISH) probes for chromosomes 1, 2, and 3. The results obtained showed that CRIPS alone did not induce CAs, while TBI caused significant increases in CAs, mostly translocations. Translocations appeared at a lower frequency in mice exposed to TBI plus CRIPS than in those exposed to TBI alone. No significant differences were observed in the frequencies of the other types of CAs (insertions, dicentrics, and fragments) visualized with FISH between these experimental groups (TBI+CRIPS vs. TBI). These results suggest that CRIPS does not appear to synergize with the clastogenicity of IR. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.mrgentox.2016.11.005 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 28010925 ● Summary page in Scopus @ Elsevier: 2-s2.0-85000351083 (DOI: 10.1016/j.mrgentox.2016.11.005, PubMed: 28010925, Elsevier: Scopus)
12.	Bing Wang, Kaoru Tanaka, Takanori Katsube, Yasuharu Ninomiya, Guillaume Vares, Qiang Liu, Akinori Morita, Tetsuo Nakajima and Mitsuru Nenoi : Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice., Journal of Radiation Research, Vol.56, No.5, 760-767, 2015. (Summary) Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice. (Tokushima University Institutional Repository) ● Metadata: 115539 (Link to Publication Site) ● Publication site (DOI): 10.1093/jrr/rrv030 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 26045492 ● Summary page in Scopus @ Elsevier: 2-s2.0-84942306654 (Tokushima University Institutional Repository: 115539, DOI: 10.1093/jrr/rrv030, PubMed: 26045492, Elsevier: Scopus)
13.	Akinori Morita, Shinya Ariyasu, Bing Wang, Tetsuo Asanuma, Takayoshi Onoda, Akiko Sawa, Kaoru Tanaka, Ippei Takahashi, Shotaro Togami, Mitsuru Nenoi, Toshiya Inaba and Shin Aoki : AS-2, a novel inhibitor of p53-dependent apoptosis, prevents apoptotic mitochondrial dysfunction in a transcription-independent manner and protects mice from a lethal dose of ionizing radiation., Biochemical and Biophysical Research Communications, Vol.450, No.4, 1498-1504, 2014. (Summary) In a previous study, we reported that some tetradentate zinc(II) chelators inhibit p53 through the denaturation of its zinc-requiring structure but a chelator, Bispicen, a potent inhibitor of in vitro apoptosis, failed to show any efficient radioprotective effect against irradiated mice because the toxicity of the chelator to mice. The unsuitability of using tetradentate chelators as radioprotectors prompted us to undertake a more extensive search for p53-inhibiting agents that are weaker zinc(II) chelators and therefore less toxic. Here, we show that an 8-hydroxyquinoline (8HQ) derivative, AS-2, suppresses p53-dependent apoptosis through a transcription-independent mechanism. A mechanistic study using cells with different p53 characteristics revealed that the suppressive effect of AS-2 on apoptosis is specifically mediated through p53. In addition, AS-2 was less effective in preventing p53-mediated transcription-dependent events than pifithrin- (PFT), an inhibitor of transcription-independent apoptosis by p53. Fluorescence visualization of the extranuclear distribution of AS-2 also supports that it is ineffective on the transcription-dependent pathway. Further investigations revealed that AS-2 suppressed mitochondrial apoptotic events, such as the mitochondrial release of intermembrane proteins and the loss of mitochondrial membrane potential, although AS-2 resulted in an increase in the mitochondrial translocation of p53 as opposed to the decrease of cytosolic p53, and did not affect the apoptotic interaction of p53 with Bcl-2. AS-2 also protected mice that had been exposed to a lethal dose of ionizing radiation. Our findings indicate that some types of bidentate 8HQ chelators could serve as radioprotectors with no substantial toxicity in vivo. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2014.07.037 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25026551 ● Summary page in Scopus @ Elsevier: 2-s2.0-84906094043 (DOI: 10.1016/j.bbrc.2014.07.037, PubMed: 25026551, Elsevier: Scopus)
14.	Shinya Ariyasu, Akiko Sawa, Akinori Morita, Kengo Hanaya, Misato Hoshi, Ippei Takahashi, Bing Wang and Shin Aoki : Design and synthesis of 8-hydroxyquinoline-based radioprotective agents., Bioorganic & Medicinal Chemistry, Vol.22, No.15, 3891-3905, 2014. (Summary) In radiation therapy, adverse side effects are often induced due to the excessive cell death that occurs in radiosensitive normal cells. The radiation-induced cell death of normal cells is caused, at least in part, by apoptosis, which undergoes via activation of p53 and increase in the p53 protein, a zinc-containing transcriptional factor, in response to cellular damage. Therefore, radioprotective drugs that can protect normal cells from radiation and thus suppress adverse side effects would be highly desirable. We report herein on the radioprotective activity of 8-hydroxyquinoline (8HQ) derivatives that were initially designed so as to interact with the Zn(2+) in p53. Indeed, the 5,7-bis(methylaminosulfonyl)-8HQ and 8-methoxyquinoline derivatives considerably protected MOLT-4 cells against -ray radiation (10Gy), accompanied by a low cytotoxicity. However, mechanistic studies revealed that the interaction of these drugs with p53 is weak and the mechanism for inhibiting apoptosis appears to be different from that of previously reported radioprotectors such as bispicen, which inhibits apoptosis via the denaturation of p53 as well as by blocking both transcription-dependent and -independent apoptotic pathways. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2014.06.017 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 25002230 ● Summary page in Scopus @ Elsevier: 2-s2.0-84905560125 (DOI: 10.1016/j.bmc.2014.06.017, PubMed: 25002230, Elsevier: Scopus)
15.	Akinori Morita, Keiji Tanimoto, Tomoki Murakami, Takeshi Morinaga and Yoshio Hosoi : Mitochondria are required for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells., Biochemical and Biophysical Research Communications, Vol.443, No.4, 1286-1290, 2014. (Summary) Ataxia-telangiectasia mutated (ATM) is a serine/threonine protein kinase that plays a central role in DNA damage response (DDR). A recent study reported that oxidized ATM can be active in the absence of DDR. However, the issue of where ATM is activated by oxidative stress remains unclear. Regarding the localization of ATM, two possible locations, namely, mitochondria and peroxisomes are possible. We report herein that ATM can be activated when exposed to hydrogen peroxide without inducing nuclear DDR in Hep G2 cells, and the oxidized cells could be subjected to subcellular fractionation. The first detergent-based fractionation experiment revealed that active, phosphorylated ATM was located in the second fraction, which also contained both mitochondria and peroxisomes. An alternative fractionation method involving homogenization and differential centrifugation, which permits the light membrane fraction containing peroxisomes to be produced, but not mitochondria, revealed that the light membrane fraction contained only traces of ATM. In contrast, the heavy membrane fraction, which mainly contained mitochondrial components, was enriched in ATM and active ATM, suggesting that the oxidative activation of ATM occurs in mitochondria and not in peroxisomes. In Rho 0-Hep G2 cells, which lack mitochondrial DNA and functional mitochondria, ATM failed to respond to hydrogen peroxide, indicating that mitochondria are required for the oxidative activation of ATM. These findings strongly suggest that ATM can be activated in response to oxidative stress in mitochondria and that this occurs in a DDR-independent manner. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2013.12.139 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24406161 ● Summary page in Scopus @ Elsevier: 2-s2.0-84893725571 (DOI: 10.1016/j.bbrc.2013.12.139, PubMed: 24406161, Elsevier: Scopus)
16.	Akinori Morita, Shinya Ariyasu, Soichiro Ohya, Ippei Takahashi, Bing Wang, Kaoru Tanaka, Takatoshi Uchida, Haruna Okazaki, Kengo Hanaya, Atsushi Enomoto, Mitsuru Nenoi, Masahiko Ikekita, Shin Aoki and Yoshio Hosoi : Evaluation of Zinc (II) chelators for inhibiting p53-mediated apoptosis., Oncotarget, Vol.4, No.12, 2439-2450, 2013. (Summary) In a previous study, we reported that sodium orthovanadate (vanadate) is the first known inhibitor that is capable of protecting mice from death from the radiation-induced gastrointestinal syndrome via its ability to block both transcription-dependent and transcription-independent p53 apoptotic pathways. In this paper, we report that vanadate has a unique activity for inducing the denaturation of p53 relative to other known radioprotective p53 inhibitors, pifithrin- (PFT) and pifithrin-µ (PFTµ). This potent radioprotective effect of vanadate prompted us to undertake a more extensive search for p53 inhibitors that can induce p53 denaturation. Based on the fact that p53 denaturation can be induced by the dissociation of a zinc ion, which is used as a structural factor of p53, we screened some zinc (II) chelators for the suppression of the DNA binding activity of p53 in vitro and the inhibition of radiation-induced p53-dependent apoptosis in MOLT-4 cells. The findings indicate that two of five zinc (II) chelators also suppressed apoptosis. Among the inhibitors tested, Bispicen (N,N'-Bis(2-pyridylmethyl)-1,2-ethanediamine) had the highest inhibition activity. A mechanistic study using cells bearing different p53 status or functions (i.e., p53-knockdown MOLT-4 transformant and its revertants, p53 mutant cells, p53-null cells), and p53-independent apoptotic stimuli revealed that the suppressive effect of Bispicen on apoptosis is specifically mediated through p53. Moreover, Bispicen, similar to vanadate, induces the denaturation of p53 as well as the blocking of both transcription-dependent and -independent apoptotic pathways. Our findings indicate that the use of zinc (II) chelators represent a new approach for protecting against radiation-induced p53-dependent apoptosis through the inhibition of p53-dependent apoptotic pathways. (Link to Publication Site) ● Publication site (DOI): 10.18632/oncotarget.1535 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 24280450 ● Summary page in Scopus @ Elsevier: 2-s2.0-84891939016 (DOI: 10.18632/oncotarget.1535, PubMed: 24280450, Elsevier: Scopus)
17.	Atsushi Enomoto, Takemichi Fukasawa, Nobuhiko Takamatsu, Michihiko Ito, Akinori Morita, Yoshio Hosoi and Kiyoshi Miyagawa : The HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin modulates radiosensitivity by downregulating serine/threonine kinase 38 via Sp1 inhibition., European Journal of Cancer, Vol.49, 3547-3558, 2013. (Summary) The ansamycin-based HSP90 inhibitor 17-AAG (17-allylamino-17-demethoxygeldanamycin) combats tumors and has been shown to modulate cellular sensitivity to radiation, prompting researchers to use 17-AAG as a radiosensitizer. 17-AAG causes the degradation of several oncogenic and signaling proteins. We previously demonstrated that oxidative stress activates serine/threonine kinase 38 (STK38), a member of the protein kinase A (PKA)/PKG/PKC-like family. In the present study, we investigated how 17-AAG affects STK38 expression, and evaluated STK38's role in the regulation of radiosensitivity. We found that 17-AAG depleted cellular STK38 and reduced STK38's kinase activity. Importantly, 17-AAG downregulated the stk38 gene expression. Deletion analysis and site-directed mutagenesis experiments demonstrated that Sp1 was required for the stk38 promoter activity. Treatment with 17-AAG inhibited Sp1's binding to the stk38 promoter by decreasing the amount of Sp1 and knocking down Sp1 reduced STK38 expression. Moreover, 17-AAG treatment or STK38 knockdown enhanced the radiosensitivity of HeLa cells. Our data provide a novel mechanism, mediated by stk38 downregulation, by which 17-AAG radiosensitizes cells. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ejca.2013.06.034 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23886587 ● Search Scopus @ Elsevier (PMID): 23886587 ● Search Scopus @ Elsevier (DOI): 10.1016/j.ejca.2013.06.034 (DOI: 10.1016/j.ejca.2013.06.034, PubMed: 23886587)
18.	Bing Wang, Kaoru Tanaka, Akinori Morita, Yasuharu Ninomiya, Kouichi Maruyama, Kazuko Fujita, Yoshio Hosoi and Mitsuru Nenoi : Sodium orthovanadate (vanadate), a potent mitigator of radiation-induced damage to the hematopoietic system in mice., Journal of Radiation Research, Vol.54, No.4, 620-629, 2013. (Summary) Previous in vitro and in vivo studies have shown that sodium orthovanadate (vanadate), an inorganic vanadium compound, could effectively suppress radiation-induced p53-mediated apoptosis via both transcription-dependent and transcription-independent pathways. As a potent radiation protector administered at a dose of 20 mg/kg body weight (20 mg/kg) prior to total body irradiation (TBI) by intra-peritoneal (ip) injection, it completely protected mice from hematopoietic syndrome and partially from gastrointestinal syndrome. In the present study, radiation mitigation effects from vanadate were investigated by ip injection of vanadate after TBI in mice. Results showed that a single administration of vanadate at a dose of 20 mg/kg markedly improved the 30-day survival rate and the peripheral blood hemogram, relieved bone marrow aplasia and decreased occurrence of the bone marrow micronucleated erythrocytes in the surviving animals. The dose reduction factor was 1.2 when a single dose of 20 mg/kg was administered 15 min after TBI in mice using the 30-day survival test as the endpoint. Results also showed that either doubling the vanadate dose (40 mg/kg) in a single administration or continuing the vanadate treatment (after a single administration at 20 mg/kg) from the following day at a dose of 5 mg/kg per day for 4 consecutive days further significantly improved the efficacy for rescuing bone marrow failure in the 30-day survival test. Taken together, these findings indicate that vanadate would be a potent mitigator suppressing the acute lethality (hematopoietic syndrome) and minimizing the detrimental effects (anhematopoiesis and delayed genotoxic effects) induced by TBI in mice. (Keyword) Animals / Bone Marrow / Erythrocytes / Female / Hematopoietic Stem Cells / Hematopoietic System / Mice / Mice, Inbred ICR / Micronucleus Tests / Radiation Injuries / Radiation-Protective Agents / Time Factors / Tumor Suppressor Protein p53 / Vanadates / Whole-Body Irradiation / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1093/jrr/rrs140 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 23349341 ● Search Scopus @ Elsevier (PMID): 23349341 ● Search Scopus @ Elsevier (DOI): 10.1093/jrr/rrs140 (DOI: 10.1093/jrr/rrs140, PubMed: 23349341)
19.	Yukihiro Furusawa, Yoshisada Fujiwara, Ali Mariame Hassan, Yoshiaki Tabuchi, Akinori Morita, Atsushi Enomoto and Takashi Kondo : Inhibition of DNA-dependent protein kinase promotes ultrasound-induced cell death including apoptosis in human leukemia cells., Cancer Letters, Vol.322, No.1, 107-112, 2012. (Summary) Ultrasound (US) has been shown to induce cell death in cancer cells; however, the underlying mechanism remains elusive. Here, we report a set of novel findings on the molecular mechanism. We found that Akt (also known as protein kinase B), a substrate of DNA-dependent protein kinase (DNA-PK), was phosphorylated in U937 cells nullified with p53 or Molt-4 cells artificially abrogated with p53 after US exposure. On the contrary, Akt phosphorylation was transiently down-regulated then recovered in Molt-4 cells harboring wild-type p53 in US-exposed cells, possibly due to a mutual regulation between p53 and Akt. Inhibition of ataxia-telangiectasia mutated (ATM) or DNA-PK revealed that DNA-PK, rather than ATM, was preferentially involved in Akt phosphorylation and cell survival after US-exposure in all cell lines. These results indicate that DNA-PK plays a protective role against US-induced cell death regardless of p53 phenotype. In conclusion, our findings provide the first delineation of the role of DNA-PK in US-induced cell death and suggest that targeting DNA-PK might be a promising strategy to augment cancer eradication by US. (Keyword) apoptosis / Cell Cycle Proteins / DNA-Activated Protein Kinase / DNA-Binding Proteins / Humans / Leukemia / phosphorylation / Protein-Serine-Threonine Kinases / Proto-Oncogene Proteins c-akt / Tumor Suppressor Protein p53 / Tumor Suppressor Proteins / U937 Cells / Ultrasonic Therapy (Link to Publication Site) ● Publication site (DOI): 10.1016/j.canlet.2012.02.020 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22366497 ● Search Scopus @ Elsevier (PMID): 22366497 ● Search Scopus @ Elsevier (DOI): 10.1016/j.canlet.2012.02.020 (DOI: 10.1016/j.canlet.2012.02.020, PubMed: 22366497)
20.	Tomohiro Ohgomori, Tomohisa Nanao, Akinori Morita and Masahiko Ikekita : Asn54-linked glycan is critical for functional folding of intercellular adhesion molecule-5., Glycoconjugate Journal, Vol.29, No.1, 47-55, 2011. (Summary) Intercellular adhesion molecule-5 (ICAM-5, telencephalin) is a dendritically polarized type I membrane glycoprotein, and promotes dendritic filopodia formation. Although we have determined the N-glycan structures of ICAM-5 in a previous report, their function is unknown. Here, we produced fifteen ICAM-5 gene constructs, in which each potential N-glycosylation site was mutated, to elucidate the function of the N-glycans of ICAM-5, and observed the effects of transfection of them on a neuronal cell line, Neuro-2a (N2a). Only the N54Q mutant, which is the mutant for the most N-terminal glycosylation site, failed to induce filopodia-like protrusions in N2a cells. Immunofluorescence staining and cell surface biotinylation revealed that N54Q ICAM-5 was confined to the ER and also could not be expressed on the cell surface. This is further supported by the biochemical evidence that almost all N-glycans of N54Q ICAM-5 were digested by Endo glycosidase H and peptide:N-glycanase, indicating that almost all of them retain high-mannose-type structures in ER. In additon, it also failed to form disulfide bonds or functional protein complexes. The stable transformants of N54Q ICAM-5 showed retarded cell growth, but it was interesting that there was no apparent ER stress, because the mutant was sequentially degraded via ER associated degradation pathway by comparing the susceptibilities of the responses to various inhibitors of this pathway in wild-type and N54Q ICAM-5 transfectants. Taken together, the Asn(54)-linked glycan is necessary for normal trafficking and function of ICAM-5, but is unassociated with ER-associated degradation of it. (Keyword) Animals / Asparagine / Cell Adhesion Molecules / Cell Line, Tumor / endoplasmic reticulum / Glycoside Hydrolases / Glycosylation / Humans / immunohistochemistry / Mannose / Mice / Microscopy, Fluorescence / Mutagenesis, Site-Directed / Nerve Tissue Proteins / Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / Polysaccharides / Protein Folding / Protein Processing, Post-Translational / Protein Transport / Pseudopodia / Rats / Transfection (Link to Publication Site) ● Publication site (DOI): 10.1007/s10719-011-9363-0 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 22187327 ● Search Scopus @ Elsevier (PMID): 22187327 ● Search Scopus @ Elsevier (DOI): 10.1007/s10719-011-9363-0 (DOI: 10.1007/s10719-011-9363-0, PubMed: 22187327)
21.	Reiko Ikeda, Masaki Kurosawa, Takazumi Okabayashi, Ayako Takei, Masamichi Yoshiwara, Tadashi Kumakura, Norio Sakai, Osamu Funatsu, Akinori Morita, Masahiko Ikekita, Yumi Nakaike and Takeo Konakahara : 3-(3-Phenoxybenzyl)amino--carboline: a novel antitumor drug targeting -tubulin., Bioorganic & Medicinal Chemistry Letters, Vol.21, No.16, 4784-4787, 2011. (Summary) 3-(3-Phenoxybenzyl)amino--carboline 2h showed extremely-high activity; the IC(50) value was 0.074 M. To verify 2h-induced cell death types, we observed the chromatin condensation, the DNA fragmentation and activated caspase-3 using Hoechst 33342, agarose electrophoresis and western blot, and suggesting 2h-induced cell death type was apoptosis. Flow cytometry showed that 2h-treated cell was induced SubG1 cell population after G2/M cell cycle arrest. In addition, using affinity chromatography and peptide mass fingerprinting, we found that interacting protein with this compound was -tubulin protein. (Keyword) Antineoplastic Agents / cell death / Cell Line, Tumor / cell proliferation and differentiation / Dose-Response Relationship, Drug / Drug Screening Assays, Antitumor / HeLa Cells / Humans / molecular structure / Stereoisomerism / structureactivity relationship / Tubulin (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmcl.2011.06.061 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21752645 ● Search Scopus @ Elsevier (PMID): 21752645 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmcl.2011.06.061 (DOI: 10.1016/j.bmcl.2011.06.061, PubMed: 21752645)
22.	Azusa Ito, Akinori Morita, Soichiro Ohya, Shinichi Yamamoto, Atsushi Enomoto and Masahiko Ikekita : Cycloheximide suppresses radiation-induced apoptosis in MOLT-4 cells with Arg72 variant of p53 through translational inhibition of p53 accumulation., Journal of Radiation Research, Vol.52, No.3, 342-350, 2011. (Summary) The human T-cell leukemia cell line MOLT-4 is highly radiosensitive, and thus it is often used as a model of p53-dependent radiation-induced apoptosis. Two branches of the p53-mediated apoptotic pathway are reported: "transcription-dependent" and "transcription-independent." However, the relative contribution of each in different types of cells is not yet clearly defined. Moreover, recent studies have shown that the codon 72 polymorphic variants of p53 show different sensitivities to apoptosis signals. The Arg72 variant has a more potent apoptosis-inducing activity in mitochondria than the Pro72 variant. Here, we initially investigated the codon 72 polymorphism of p53 in MOLT-4 cells. Analysis of the p53 exon 4 genomic DNA sequence, which includes codon 72, revealed that MOLT-4 cells are homozygous for the allele encoding Arg72. We next investigated the involvement of the transcription-independent function of p53 using an RNA synthesis inhibitor, actinomycin D (ActD), and a protein synthesis inhibitor, cycloheximide (CHX), and found that the apoptosis was suppressed by CHX but not by ActD. We also revealed that the suppressive effect of CHX on apoptosis was specifically mediated by p53, using a p53-knockdown MOLT-4 transfectant. Furthermore, the suppressive effect of CHX on apoptosis was highly correlated with the suppression of p53 protein accumulation, and less correlated with the suppression of p53 target genes expression. These results indicated that p53 transactivation is not necessary to induce apoptosis, and that p53 protein accumulation itself is both necessary and sufficient to do so. (Keyword) apoptosis / Arginine / Cell Line, Tumor / Cycloheximide / Genetic Variation / Humans / Leukemia, T-Cell / Protein Transport / signal transduction / Tumor Suppressor Protein p53 (Link to Publication Site) ● Publication site (DOI): 10.1269/jrr.10151 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 21467739 ● CiNii @ National Institute of Informatics (CRID): 1390282680193524864 ● Search Scopus @ Elsevier (PMID): 21467739 ● Search Scopus @ Elsevier (DOI): 10.1269/jrr.10151 (DOI: 10.1269/jrr.10151, PubMed: 21467739, CiNii: 1390282680193524864)
23.	Anlifeire A, Hatori M, Akinori Morita, Shiina I, Nakata K, Tosaki Y, Wang Y.-W., Ikekita M and Li G : Ridaifen-G induces caspase-independent atypical cell death., Chinese Journal of Cell Biology, Vol.33, No.6, 635-644, 2011. (Keyword) apoptosis / mitochondria / caspase
24.	Kotaro Suzuki, Tomomi Kobayashi, Osamu Funatsu, Akinori Morita and Masahiko Ikekita : Activin A induces neuronal differentiation and survival via ALK4 in a SMAD-independent manner in a subpopulation of human neuroblastomas., Biochemical and Biophysical Research Communications, Vol.394, No.3, 639-645, 2010. (Summary) Activin A is a multifunctional homo-dimeric protein that belongs to the transforming growth factor (TGF)-beta superfamily. In neurons, activin has neuroprotective effects both in vitro and in vivo, but it inhibits neuronal differentiation in some cell lines. Here we report that activin A can promote neuronal differentiation in particular cases. We examined activin A-induced neuronal differentiation and survival in a selected subpopulation of a human neuroblastoma cell line, SK-N-SH, grown in low-serum (differentiation-inducing) conditions. Activin A caused dramatic neurite outgrowth, and increased the expression of neuronal markers and the transactivation of dopamine beta-hydroxylase. We demonstrated that the activin A signal is transduced through the activin A type 1 receptor, ALK4, and transactivates several TGF-beta target genes in a SMAD-independent manner. That is, activin A did not induce the phosphorylation of SMAD2/3, the interaction of SMAD2/3 with SMAD4, the binding of SMAD2/3 to the promoter of TGF-beta target genes, or the accumulation of SMAD2/3 in the nucleus. These results suggest that, in particular cases, activin A can induce neuronal differentiation and support neuronal survival in vitro. These findings may reflect previously unknown functions of activin A in neuronal cells in vivo. (Keyword) Activin Receptors, Type I / Activins / Adult / Cell Line, Tumor / Cell Nucleus / Cell Survival / Humans / Male / Neurogenesis / Neurons / phosphorylation / Promoter Regions, Genetic / Smad Proteins / Smad2 Protein / Smad3 Protein / Smad4 Protein / Transcriptional Activation / Transforming Growth Factor beta (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2010.03.039 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20226172 ● Search Scopus @ Elsevier (PMID): 20226172 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2010.03.039 (DOI: 10.1016/j.bbrc.2010.03.039, PubMed: 20226172)
25.	Ryosuke Ohshima, Masanori Kitamura, Akinori Morita, Motoo Shiro, Yasuyuki Yamada, Masahiko Ikekita, Eiichi Kimura and Shin Aoki : Design and synthesis of a fluorescent probe for Zn2+, 5,7-bis(N,N-dimethylaminosulfonyl)-8-hydroxyquinoline-pendant 1,4,7,10-tetraazacyclododecane and Zn2+-dependent hydrolytic and Zn2+-independent photochemical reactivation of its benzenesulfonyl-caged derivative., Inorganic Chemistry, Vol.49, No.3, 888-899, 2010. (Summary) We previously reported on a 8-quinolinol-pendant cyclen (L(5)) as a Zn(2+) fluorophore (cyclen = 1,4,7,10-tetraazacyclododecane) and its caged derivative, 8-(benzenesulfonyloxy)-5-(N,N-dimethylaminosulfonyl)quinolin-2-ylmethyl-pendant cyclen (BS-caged-L(5)), which can be reactivated by hydrolysis of benzenesulfonyl group upon complexation with Zn(2+) at neutral pH to give a 1:1 Zn(2+)-L(5) complex (Zn(H(-1)L(5))). We report herein on the synthesis of 5,7-bis(N,N-dimethylaminosulfonyl)-8-hydroxyquinolin-2-ylmethyl-pendant cyclen (L(6)) and its caged derivative (BS-caged-L(6)) for more sensitive and more efficient cell-membrane permeability than those of L(5) and BS-caged-L(5). By potentiometric pH, (1)H NMR, and UV-vis spectroscopic titrations, the deprotonation constants pK(a1)-pK(a6) of H(5)L(6) were determined to be <2, <2, <2, 2.5 +/- 0.1 (for the 8-OH group of the quinoline moiety), 9.7 +/- 0.1, and 10.8 +/- 0.1 at 25 degrees C with I = 0.1 (NaNO(3)). The results of (1)H NMR, potentiometric pH, UV-vis, and fluorescent titrations showed that L(6) rapidly forms a 1:1 complex with Zn(2+) (Zn(H(-1)L(6))), the dissociation constant of which is 50 fM at pH 7.4. The fluorescent emission of Zn(H(-1)L(6)) at 478 nm is 32 times as large as that of L(6) (excitation at 370 nm), and the fluorescent quantum yield of Zn(H(-1)L(6)) (Phi(F) = 0.41) is much greater than that of Zn(H(-1)L(5)) (Phi(F) = 0.044). The BS-caged-L(6) was reactivated by hydrolysis of the benzenesulfonyl moiety more rapidly (completes in 30 min at pH 7.4 at 37 degrees C) than BS-caged-L(5), presumably enabling the practical detection of Zn(2+) in sample solutions and living cells. The photochemical deprotection of BS-caged-L(6) and the cell membrane permeability of L(6) and BS-caged-L(6) are also described. (Keyword) Fluorescent Dyes / Hydrolysis / Ligands / molecular structure / Organometallic Compounds / photochemistry / Sulfones / zinc (Link to Publication Site) ● Publication site (DOI): 10.1021/ic901279t (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20039701 ● Search Scopus @ Elsevier (PMID): 20039701 ● Search Scopus @ Elsevier (DOI): 10.1021/ic901279t (DOI: 10.1021/ic901279t, PubMed: 20039701)
26.	N Sasano, A Enomoto, Y Hosoi, Y Katsumura, Y Matsumoto, Akinori Morita, K Shiraishi, K Miyagawa, H Igaki and K Nakagawa : Edaravone, a known free radical scavenger, enhances X-ray-induced apoptosis at low concentrations., Cancer Letters, Vol.293, No.1, 52-57, 2010. (Summary) Edaravone has been reported to have a radioprotective effect at high concentrations. We now report that a lower dose of edaravone enhanced X-ray-induced apoptosis of some cell lines harboring p53 wild-type status, such as MOLT-4, Nalm-6, and HepG2. The knock-down of p53 using siRNA in MOLT-4 cells abolished the radiosensitizing effect of edaravone. Enhanced phosphorylations of p53 at Ser 15 and Ser 20 and up-regulation of PUMA, a p53 target protein, were observed after X-irradiation in the presence of edaravone. We conclude that the low dose of edaravone sensitized cells to X-irradiation by promoting the p53-dependent apoptotic signaling pathway. (Keyword) Antipyrine / apoptosis / Cell Line, Tumor / Dose-Response Relationship, Drug / Free Radical Scavengers / Gene Knockdown Techniques / Hep G2 Cells / Humans / Leukemia, T-Cell / Radiation-Sensitizing Agents / reactive oxygen species / Transfection / Tumor Cells, Cultured / Tumor Suppressor Protein p53 / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1016/j.canlet.2009.12.020 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20092938 ● Search Scopus @ Elsevier (PMID): 20092938 ● Search Scopus @ Elsevier (DOI): 10.1016/j.canlet.2009.12.020 (DOI: 10.1016/j.canlet.2009.12.020, PubMed: 20092938)
27.	Akinori Morita, Shinichi Yamamoto, Bing Wang, Kaoru Tanaka, Norio Suzuki, Shin Aoki, Azusa Ito, Tomohisa Nanao, Soichiro Ohya, Minako Yoshino, Jin Zhu, Atsushi Enomoto, Yoshihisa Matsumoto, Osamu Funatsu, Yoshio Hosoi and Masahiko Ikekita : Sodium orthovanadate inhibits p53-mediated apoptosis., Cancer Research, Vol.70, No.1, 257-265, 2010. (Summary) Sodium orthovanadate (vanadate) inhibits the DNA-binding activity of p53, but its precise effects on p53 function have not been examined. Here, we show that vanadate exerts a potent antiapoptotic activity through both transcription-dependent and transcription-independent mechanisms relative to other p53 inhibitors, including pifithrin (PFT) alpha. We compared the effects of vanadate to PFTalpha and PFTmicro, an inhibitor of transcription-independent apoptosis by p53. Vanadate suppressed p53-associated apoptotic events at the mitochondria, including the loss of mitochondrial membrane potential, the conformational change of Bax and Bak, the mitochondrial translocation of p53, and the interaction of p53 with Bcl-2. Similarly, vanadate suppressed the apoptosis-inducing activity of a mitochondrially targeted temperature-sensitive p53 in stable transfectants of SaOS-2 cells. In radioprotection assays, which rely on p53, vanadate completely protected mice from a sublethal dose of 8 Gy and partially from a lethal dose of 12 Gy. Together, our findings indicated that vanadate effectively suppresses p53-mediated apoptosis by both transcription-dependent and transcription-independent pathways, and suggested that both pathways must be inhibited to completely block p53-mediated apoptosis. (Keyword) Animals / apoptosis / Benzothiazoles / Blotting, Western / Cell Line / Female / Flow Cytometry / Humans / Immunoprecipitation / Mice / Mice, Inbred ICR / Radiation-Protective Agents / Sulfonamides / Toluene / Transfection / Tumor Suppressor Protein p53 / Vanadates (Link to Publication Site) ● Publication site (DOI): 10.1158/0008-5472.CAN-08-3771 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 20048077 ● Search Scopus @ Elsevier (PMID): 20048077 ● Search Scopus @ Elsevier (DOI): 10.1158/0008-5472.CAN-08-3771 (DOI: 10.1158/0008-5472.CAN-08-3771, PubMed: 20048077)
28.	Tomohiro Ohgomori, Osamu Funatsu, Syu-ichi Nakaya, Akinori Morita and Masahiko Ikekita : Structural study of the N-glycans of intercellular adhesion molecule-5 (telencephalin)., Biochimica et Biophysica Acta (BBA) - General Subjects, Vol.1790, No.12, 1611-1623, 2009. (Summary) Intercellular adhesion molecule-5 (ICAM-5, telencephalin) is a dendritically polarized membrane glycoprotein expressed in tissues distinct from those expressing other ICAMs. Here, we determined the N-glycan structure of ICAM-5 purified from adult rat brain and compared it with that of other ICAMs. N-glycans were released by N-glycosidase F digestion and labeled with p-amino benzoic octylester (ABOE). ABOE-labeled glycans were analyzed by high performance liquid chromatography (HPLC) and mass spectrometry. The N-glycans obtained from rat brain ICAM-5 consisted of approximately 85% neutral, 10.2% sialylated-only, 2.8% sulfated-only, and 1.2% sialylated and sulfated glycans. Compared with the N-glycan structures of human ICAM-1 expressed in CHO cells, HEK cells, or mouse myeloma cells and ICAM-3 isolated from human T-cells, rat brain ICAM-5 had less highly branched glycans, sialylated glycans, and N-acetyllactosamine structures. In contrast, high-mannose-type N-glycans and Lewis X were more commonly found in rat brain ICAM-5 than in human ICAM-1 expressed in CHO cells, HEK cells, or mouse myeloma cells and ICAM-3 isolated from human T-cells. In addition, sulfated glycans contained GlcNAc 6-O-sulfate on the non-reducing terminal side. Our data will be important for the elucidation of the roles of the N-glycans expressed in neural cells, including those present on ICAM-5. (Keyword) 4-Aminobenzoic Acid / Animals / CHO Cells / Carbohydrate Sequence / Cell Adhesion Molecules / Chromatography, High Pressure Liquid / Cricetinae / Cricetulus / Humans / Molecular Conformation / Molecular Sequence Data / Nerve Tissue Proteins / Neural Cell Adhesion Molecules / Neurons / Polysaccharides / Rabbits / Rats / Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Tandem Mass Spectrometry / para-Aminobenzoates (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbagen.2009.08.012 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 19733219 ● Search Scopus @ Elsevier (PMID): 19733219 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbagen.2009.08.012 (DOI: 10.1016/j.bbagen.2009.08.012, PubMed: 19733219)
29.	Yasuyuki Yamada, Yumiko Tomiyama, Akinori Morita, Masahiko Ikekita and Shin Aoki : BODIPY-based fluorescent redox potential sensors that utilize reversible redox properties of flavin., ChemBioChem, Vol.9, No.6, 853-856, 2008. (Keyword) Boron Compounds / electrochemistry / Flavins / Fluorescence / Fluorescent Dyes / HeLa Cells / Humans / oxidation and reduction / photochemistry (Link to Publication Site) ● Publication site (DOI): 10.1002/cbic.200700718 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18338353 ● Search Scopus @ Elsevier (PMID): 18338353 ● Search Scopus @ Elsevier (DOI): 10.1002/cbic.200700718 (DOI: 10.1002/cbic.200700718, PubMed: 18338353)
30.	Kouji Kuramochi, Shunsuke Yukizawa, Seiki Ikeda, Takashi Sunoki, Satoshi Arai, Rie Matsui, Akinori Morita, Yoshiyuki Mizushina, Kengo Sakaguchi, Fumio Sugawara, Masahiko Ikekita and Susumu Kobayashi : Syntheses and applications of fluorescent and biotinylated epolactaene derivatives: Epolactaene and its derivative induce disulfide formation., Bioorganic & Medicinal Chemistry, Vol.16, No.9, 5039-5049, 2008. (Summary) Epolactaene, isolated from cultured Penicillium sp. BM 1689-P mycelium, induces neurite outgrowth and arrests the cell cycle of the human neuroblastoma cell line, SH-SY5Y, at the G1 phase. We have found that epolactaene and its derivatives induce apoptosis in the human leukemia B-cell line, BALL-1. In this study, we prepared fluorescent and biotinylated epolactaene derivatives. We characterized the cellular location and the identification of BALL-1 proteins that reacted with these compounds. The results obtained from the reaction of epolactaene or its derivative with N-acetylcysteine methyl ester indicate that these compounds induce the disulfide formation and the alpha-position of the epoxylactam core is the reactive site. (Keyword) Acetylcysteine / Biotin / Biotinylation / cell death / Disulfides / Drug Screening Assays, Antitumor / Epoxy Compounds / Fluorescence / Humans / molecular structure / Polyenes / Stereoisomerism / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bmc.2008.03.029 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 18375133 ● Search Scopus @ Elsevier (PMID): 18375133 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bmc.2008.03.029 (DOI: 10.1016/j.bmc.2008.03.029, PubMed: 18375133)
31.	A Enomoto, N Kido, M Ito, Akinori Morita, Y Matsumoto, N Takamatsu, Y Hosoi and K Miyagawa : Negative regulation of MEKK1/2 signaling by serine-threonine kinase 38 (STK38)., Oncogene, Vol.27, No.13, 1930-1938, 2007. (Summary) Mitogen-activated protein kinases (MAPKs) are activated through the kinase cascades of MAPK, MAPK kinase (MAPKK) and MAPKK kinase (MAPKKK). MAPKKKs phosphorylate and activate their downstream MAPKKs, which in turn phosphorylate and activate their downstream MAPKs. MAPKKK proteins relay upstream signals through the MAPK cascades to induce cellular responses. However, the molecular mechanisms by which given MAPKKKs are regulated remain largely unknown. Here, we found that serine-threonine protein kinase 38, STK38, physically interacts with the MAPKKKs MEKK1 and MEKK2 (MEKK1/2). The carboxy terminus, including the catalytic domain, but not the amino terminus of MEKK1/2 was necessary for the interaction with STK38. STK38 inhibited MEKK1/2 activation without preventing MEKK1/2 binding to its substrate, SEK1. Importantly, STK38 suppressed the autophosphorylation of MEKK2 without interfering with MEKK2 dimer formation, and converted MEKK2 from its phosphorylated to its nonphosphorylated form. The negative regulation of MEKK1/2 was not due to its phosphorylation by STK38. On the other hand, stk38 short hairpin RNA enhanced sorbitol-induced activation of MEKK2 and phosphorylation of the downstream MAPKKs, MKK3/6. Taken together, our results indicate that STK38 negatively regulates the activation of MEKK1/2 by direct interaction with the catalytic domain of MEKK1/2, suggesting a novel mechanism of MEKK1/2 regulation. (Keyword) Animals / Blotting, Western / COS Cells / Cells, Cultured / Cercopithecus aethiops / Dimerization / Gene Expression Profiling / Gene Expression Regulation / Humans / Immunoprecipitation / Indicators and Reagents / MAP Kinase Kinase 4 / MAP Kinase Kinase Kinase 1 / MAP Kinase Kinase Kinases / Oligonucleotide Array Sequence Analysis / phosphorylation / Protein-Serine-Threonine Kinases / RNA, Small Interfering / signal transduction / Sorbitol (Link to Publication Site) ● Publication site (DOI): 10.1038/sj.onc.1210828 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 17906693 ● Search Scopus @ Elsevier (PMID): 17906693 ● Search Scopus @ Elsevier (DOI): 10.1038/sj.onc.1210828 (DOI: 10.1038/sj.onc.1210828, PubMed: 17906693)
32.	Akinori Morita, J Zhu, N Suzuki, A Enomoto, Y Matsumoto, M Tomita, T Suzuki, K Ohtomo and Y Hosoi : Sodium orthovanadate suppresses DNA damage-induced caspase activation and apoptosis by inactivating p53., Cell Death and Differentiation, Vol.13, No.3, 499-511, 2006. (Summary) We previously reported that p42/SETbeta is a substrate for caspase-7 in irradiated MOLT-4 cells, and that treating the cells with sodium orthovanadate (vanadate) inhibits p42/SETbeta's caspase-mediated cleavage. Here, we initially found that the inhibitory effect of vanadate was due to the suppression of caspase activation but not of caspase activity. Further investigations revealed that vanadate suppressed upstream of apoptotic events, such as the loss of mitochondrial membrane potential, the conformational change of Bax, and p53 transactivation, although the accumulation, total phosphorylation, and phosphorylation of six individual sites of p53 were not affected. Importantly, vanadate suppressed p53-dependent apoptosis, but not p53-independent apoptosis. Finally, gel-shift and chromatin immunoprecipitation assays conclusively demonstrated that vanadate inhibits the DNA-binding activity of p53. Vanadate is conventionally used as an inhibitor of protein tyrosine phosphatases (PTPs); however, we recommend that the influence of vanadate not only on PTPs but also on p53 be considered before using it. (Keyword) apoptosis / Caspase Inhibitors / Caspases / Cell Line, Tumor / DNA Damage / Enzyme Activation / Humans / Membrane Potentials / mitochondria / Tumor Suppressor Protein p53 / Vanadates / bcl-2-Associated X Protein (Link to Publication Site) ● Publication site (DOI): 10.1038/sj.cdd.4401768 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16138109 ● Search Scopus @ Elsevier (PMID): 16138109 ● Search Scopus @ Elsevier (DOI): 10.1038/sj.cdd.4401768 (DOI: 10.1038/sj.cdd.4401768, PubMed: 16138109)
33.	Zhiping Li, Yoshio Hosoi, Keshong Cai, Yuji Tanno, Yoshihisa Matsumoto, Atsushi Enomoto, Akinori Morita, Keiichi Nakagawa and Kiyoshi Miyagawa : Src tyrosine kinase inhibitor PP2 suppresses ERK1/2 activation and epidermal growth factor receptor transactivation by X-irradiation., Biochemical and Biophysical Research Communications, Vol.341, No.2, 363-368, 2006. (Summary) Exposure of MDA-MB-468 cells to ionizing radiation (IR) caused biphasic activation of ERK as indicated by its phosphorylation at Thr202/Tyr204. Specific epidermal growth factor receptor (EGFR) inhibitor AG1478 and specific Src inhibitor PP2 inhibited IR-induced ERK1/2 activation but phosphatidylinositol-3 kinase inhibitor wortmannin did not. IR caused EGFR tyrosine phosphorylation, whereas it did not induce EGFR autophosphorylation at Tyr992, Tyr1045, and Tyr1068 or Src-dependent EGFR phosphorylation at Tyr845. SHP-2, which positively regulates EGFR/Ras/ERK signaling cascade, became activated by IR as indicated by its phosphorylation at Tyr542. This activation was inhibited by PP2 not by AG1478, which suggests Src-dependent activation of SHP-2. Src and PTPalpha, which positively regulates Src, became activated as indicated by phosphorylation at Tyr416 and Tyr789, respectively. These data suggest that IR-induced ERK1/2 activation involves EGFR through a Src-dependent pathway that is distinct from EGFR ligand activation. (Keyword) Androstadienes / Cell Line, Tumor / Cells, Cultured / Dose-Response Relationship, Radiation / Enzyme Activation / Enzyme Inhibitors / Epidermal Growth Factor / Extracellular Signal-Regulated MAP Kinases / Guanosine Triphosphate / Humans / Immunoblotting / Immunoprecipitation / infrared rays / Intracellular Signaling Peptides and Proteins / Kinetics / Ligands / Mitogen-Activated Protein Kinase 1 / Mitogen-Activated Protein Kinase 3 / phosphorylation / Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Protein Tyrosine Phosphatases / Pyrimidines / Quinazolines / Radiation, Ionizing / signal transduction / temperature / Time Factors / Transcriptional Activation / Tyrosine / Tyrphostins / X-Rays / src-Family Kinases (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2005.12.193 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 16414009 ● Summary page in Scopus @ Elsevier: 2-s2.0-31444451032 (DOI: 10.1016/j.bbrc.2005.12.193, PubMed: 16414009, Elsevier: Scopus)
34.	Shingo Komiyama, Sachiko Taniguchi, Yoshihisa Matsumoto, Eri Tsunoda, Takayo Ohto, Yuka Suzuki, Hong-Lan Yin, Masanori Tomita, Atsushi Enomoto, Akinori Morita, Takahiko Suzuki, Kuni Ohtomo, Yoshio Hosoi and Norio Suzuki : Potentiality of DNA-dependent protein kinase to phosphorylate Ser46 of human p53., Biochemical and Biophysical Research Communications, Vol.323, No.3, 816-822, 2004. (Summary) DNA damage induces accumulation and activation of p53 via various posttranslational modifications. Among them, several lines of evidence indicated the phosphorylation of Ser46 as an important mediator of DNA damage-induced apoptosis but the responsible kinase remains to be clarified, especially in the case of ionizing radiation (IR). Here we showed that DNA-dependent protein kinase (DNA-PK) could phosphorylate Ser46 of p53 in addition to reported phosphorylation sites Ser15 and Ser37. However, IR-induced phosphorylation of Ser46 was seen even in M059J, a human glioma cell line lacking DNA-PKcs, and it was, at most, only slightly less than in control M059K. On the other hand, a related kinase ataxia-telangiectasia mutated (ATM), which was shown to be essential for IR-induced phosphorylation of Ser46, could poorly phosphorylate Ser46 by itself. These results collectively suggested two pathways for IR-induced phosphorylation of Ser46, i.e., direct phosphorylation by DNA-PK and indirect phosphorylation via ATM. (Keyword) Binding Sites / Cell Line, Tumor / DNA / DNA Damage / DNA-Activated Protein Kinase / DNA-Binding Proteins / Humans / Nuclear Proteins / phosphorylation / Protein Binding / Protein-Serine-Threonine Kinases / Serine / Tumor Suppressor Protein p53 (Link to Publication Site) ● Publication site (DOI): 10.1016/j.bbrc.2004.08.161 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15381073 ● Search Scopus @ Elsevier (PMID): 15381073 ● Search Scopus @ Elsevier (DOI): 10.1016/j.bbrc.2004.08.161 (DOI: 10.1016/j.bbrc.2004.08.161, PubMed: 15381073)
35.	Lan Hong Yin, Yuka Suzuki, Yoshihisa Matsumoto, Masanori Tomita, Yoshiya Furusawa, Atsushi Enomoto, Akinori Morita, Mizuho Aoki, Fumio Yatagai, Takahiko Suzuki, Yoshio Hosoi, Kuni Ohtomo and Norio Suzuki : Radiosensitization by hyperthermia in the chicken B-lymphocyte cell line DT40 and its derivatives lacking nonhomologous end joining and/or homologous recombination pathways of DNA double-strand break repair., Radiation Research, Vol.162, No.4, 433-441, 2004. (Summary) Hyperthermia has a radiosensitizing effect, which is one of the most important biological bases for its use in cancer therapy with radiation. Although the mechanism of this effect has not been clarified in molecular terms, possible involvement of either one or both of two major DNA double-strand break (DSB) repair pathways, i.e. nonhomologous end joining (NHEJ) and homologous recombination (HR), has been speculated. To test this possibility, we examined cells of the chicken B-lymphocyte cell line DT40 and its derivatives lacking NHEJ and/or HR: KU70(-/-), DNA-PKcs(-/-/-), RAD54(-/-) and KU70(-/-)/RAD54(-/-). Radiosensitization by hyperthermia could be seen in all of the mutants, including KU70(-/-)/RAD54(-/-), which lacked both NHEJ and HR. Therefore, radiosensitization by hyperthermia cannot be explained simply by its inhibitory effects, if any, on NHEJ and/or HR alone. However, in NHEJ-defective KU70(-/-) and DNA-PKcs(-/-/-), consisting of two subpopulations with distinct radiosensitivity, the radiosensitive subpopulation, which is considered to be cells in G(1) and early S, was not sensitized. Substantial sensitization was seen only in the radioresistant subpopulation, which is considered to be cells in late S and G(2), capable of repairing DSBs through HR. This observation did not exclude possible involvement of NHEJ in G(1) and early S phase and also suggested inhibitory effects of hyperthermia on HR. Thus partial contribution of NHEJ and HR in radiosensitization by hyperthermia, especially that depending on the cell cycle stage, remains to be considered. (Keyword) Animals / B-Lymphocytes / Cell Line / Chickens / DNA / DNA Damage / DNA Repair / Dose-Response Relationship, Radiation / G1 Phase / G2 Phase / Hot Temperature / Humans / Hyperthermia, Induced / Mice / Recombination, Genetic / S Phase / temperature / Time Factors / Transgenes / U937 Cells / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1667/RR3239 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15447039 ● Search Scopus @ Elsevier (PMID): 15447039 ● Search Scopus @ Elsevier (DOI): 10.1667/RR3239 (DOI: 10.1667/RR3239, PubMed: 15447039)
36.	Yoshio Hosoi, Yoshihisa Matsumoto, Atsushi Enomoto, Akinori Morita, Joseph Green, Keiichi Nakagawa, Kiyoshi Naruse and Norio Suzuki : Suramin Sensitizes cells to ionizing radiation by inactivating DNA-dependent protein kinase., Radiation Research, Vol.162, No.3, 308-314, 2004. (Summary) Here we report that suramin sensitizes LM217, MDA-MB-468, T98G and A431 cells to ionizing radiation. Suramin sensitized cells to X radiation in a dose-dependent fashion, and longer exposure to suramin before X irradiation resulted in more efficient sensitization. The dose-modifying factors calculated from the survival curves were 1.18 in LM217 cells and 1.37 in MDA-MB-468 cells. Suramin did not sensitize Scid cells that had no DNA-dependent protein kinase activity. Suramin inhibited DNA-dependent protein kinase activity in vitro and in vivo. The concentration of suramin resulting in 50% inhibition in vitro was 1.7 microM in LM217 cells and 2.4 microM in MDA-MB-468 cells. Exposure of LM217 and MDA-MB-468 cells to suramin did not affect the level of Ku70 (G22P1) or Ku80 (XRCC5), but it increased the level of DNA-PKcs(PRKDC). Suramin did not sensitize LM217 or MDA-MB-468 cells to UV radiation. Suramin's effects were not caused by accumulation of cells in a specific phase of the cell cycle. These results suggest that suramin sensitizes cells to ionizing radiation by inhibiting DNA-dependent protein kinase activity. (Keyword) Cell Line / Cell Line, Tumor / Cell Survival / DNA-Activated Protein Kinase / DNA-Binding Proteins / Dose-Response Relationship, Drug / Dose-Response Relationship, Radiation / Enzyme Activation / Fibroblasts / Humans / Neoplasms / Nuclear Proteins / Protein-Serine-Threonine Kinases / Radiation Tolerance / Radiation, Ionizing / Radiation-Sensitizing Agents / Suramin / Ultraviolet Rays / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1667/RR3217 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15378840 ● Search Scopus @ Elsevier (PMID): 15378840 ● Search Scopus @ Elsevier (DOI): 10.1667/RR3217 (DOI: 10.1667/RR3217, PubMed: 15378840)
37.	Yoshio Hosoi, Toshiaki Watanabe, Keiichi Nakagawa, Yoshihisa Matsumoto, Atsushi Enomoto, Akinori Morita, Hirokazu Nagawa and Norio Suzuki : Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer., International Journal of Oncology, Vol.25, No.2, 461-468, 2004. (Summary) Tumor tissues and adjacent normal tissues in 12 colorectal cancers were examined for quantitative differences in: i) activity of DNA-dependent protein kinase (DNA-PK), which functions in DNA double-strand breads repair, and ii) protein and mRNA levels of Ku70, Ku80, DNA-PKcs and transcriptional factor Sp1. DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were significantly higher in the tumor tissues compared with the normal tissues. Significant correlations between DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were observed. Because Ku80 and DNA-PKcs have consensus Sp1 recognition elements in their promoter region, the DNA sequence of Ku70 promoter region was analyzed. Analysis of Ku70 promoter region reveled that Ku70 gene has consensus Sp1 recognition elements in its promoter region. mRNA levels of Ku70, Ku80 and DNA-PKcs were correlated with one another, and significant correlations between Sp1 protein level and mRNA levels of Ku70 and Ku80 were observed. These results suggest that DNA-PK activity and protein- and mRNA-levels of Ku70, Ku80 and DNA-PKcs were elevated in tumor tissues in patients with colorectal cancer because of elevated Sp1 protein levels in tumor tissues. (Keyword) Adenocarcinoma / Adult / Aged / Aged, 80 and over / Antigens, Nuclear / Base Sequence / Cell Line / Colorectal Neoplasms / DNA-Activated Protein Kinase / DNA-Binding Proteins / Female / Gene Expression Regulation, Neoplastic / Humans / Male / Middle Aged / Molecular Sequence Data / Nuclear Proteins / Promoter Regions, Genetic / Protein-Serine-Threonine Kinases / RNA, Messenger / Sp1 Transcription Factor / Tissue Extracts / Up-Regulation (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 15254745 ● Search Scopus @ Elsevier (PMID): 15254745 (PubMed: 15254745)
38.	N Umeda, Y Matsumoto, H-L Yin, M Tomita, A Enomoto, Akinori Morita, T Mizukoshi, K Sakai, Y Hosoi and N Suzuki : Difference in the heat sensitivity of DNA-dependent protein kinase activity among mouse, hamster and human cells., International Journal of Radiation Biology, Vol.79, No.8, 671-680, 2003. (Summary) The heat sensitivity of DNA-PK was clearly different among mouse, hamster and human cells. The results suggested a possibility that the role of DNA-PK inactivation in hyperthermic radiosensitization might be variable, depending on cells, and would reinforce the warning that the direct extrapolation of data from rodent cells might lead to overestimation of the effectiveness of hyperthermia on human cancer. (Keyword) Animals / CHO Cells / Cricetinae / DNA-Activated Protein Kinase / DNA-Binding Proteins / Hot Temperature / Humans / Mice / Nuclear Proteins / Protein-Serine-Threonine Kinases / Radiation Tolerance / Species Specificity (Link to Publication Site) ● Publication site (DOI): 10.1080/09553000310001596959 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14555350 ● Search Scopus @ Elsevier (PMID): 14555350 ● Search Scopus @ Elsevier (DOI): 10.1080/09553000310001596959 (DOI: 10.1080/09553000310001596959, PubMed: 14555350)
39.	A Enomoto, N Suzuki, Y Kang, K Hirano, Y Matsumoto, J Zhu, Akinori Morita, Y Hosoi, K Sakai and H Koyama : Decreased c-Myc expression and its involvement in X-ray-induced apoptotic cell death of human T-cell leukaemia cell line MOLT-4., International Journal of Radiation Biology, Vol.79, No.8, 589-600, 2003. (Summary) A decrease of c-Myc protein was considered important in X-ray-induced apoptotic cell death of MOLT-4 cells; activation of the JNK pathway caused reduction in the amounts of c-myc mRNA and c-Myc protein, and finally induced apoptotic cell death. (Keyword) Anisomycin / Apoptosis / Cell Line, Tumor / Cell Survival / Humans / Leukemia, T-Cell / Mitogen-Activated Protein Kinase 8 / Mitogen-Activated Protein Kinases / Proto-Oncogene Proteins c-myc / RNA, Messenger / Sphingosine / Tumor Suppressor Protein p53 / X-Rays (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 14555342 ● Search Scopus @ Elsevier (PMID): 14555342 (PubMed: 14555342)
40.	Atsushi Enomoto, Norio Suzuki, Akinori Morita, Michihiko Ito, Qing Chang Liu, Yoshihisa Matsumoto, Katsuji Yoshioka, Tadayoshi Shiba and Yoshio Hosoi : Caspase-mediated cleavage of JNK during stress-induced apoptosis., Biochemical and Biophysical Research Communications, Vol.306, No.4, 837-842, 2003. (Summary) The c-Jun N-terminal kinases (JNKs) are a subfamily of the mitogen-activated protein kinases (MAPKs). The JNKs are encoded by three separate genes (jnk1, jnk2, and jnk3), which are spliced alternatively to create 10 JNK isoforms that are either p46 or p54 in size. In this study, we found that the p52 form of JNK emerged in human leukemia MOLT-4 or U937 cells following X-irradiation or heat treatment. The accumulation of p52 coincided with the reduction of p54 JNK. On the other hand, the amounts of p46 JNK did not change by X-irradiation. Induction of the p52 form of JNK also paralleled the appearance of the active form of caspase-3 and was suppressed by a caspase-specific inhibitor, Ac-DEVD-CHO, but not by Ac-YVAD-CHO. In vitro cleavage assays indicated that recombinant human JNK1beta2 and JNK2beta2 were cleaved by caspase-3, and that the mutation of aspartic acid at position 413 of JNK1beta2 or 410 of JNK2beta2 to alanine abolished the cleavage. Altogether, our results demonstrated that p54 JNKs, at least JNK1beta2 and JNK2beta2, were new selective targets of caspases in JNK splicing variants, and suggested that the p52 form could serve as a marker of apoptosis. (Keyword) Alternative Splicing / apoptosis / Blotting, Western / Caspase 3 / Caspases / Cell Line / Enzyme Inhibitors / Gene Deletion / Humans / Mitogen-Activated Protein Kinase 8 / Mitogen-Activated Protein Kinase 9 / Mitogen-Activated Protein Kinases / Oligopeptides / Open Reading Frames / phosphorylation / Plasmids / Protein Isoforms / Recombinant Proteins / Reverse Transcriptase Polymerase Chain Reaction / Time Factors / Tumor Cells, Cultured / U937 Cells / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1016/S0006-291X(03)01050-7 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 12821118 ● Search Scopus @ Elsevier (PMID): 12821118 ● Search Scopus @ Elsevier (DOI): 10.1016/S0006-291X(03)01050-7 (DOI: 10.1016/S0006-291X(03)01050-7, PubMed: 12821118)
41.	Y Hosoi, Y Matsumoto, M Tomita, A Enomoto, Akinori Morita, K Sakai, N Umeda, H-J Zhao, K Nakagawa, T Ono and N Suzuki : Phosphorothioate oligonucleotides, suramin and heparin inhibit DNA-dependent protein kinase activity., British Journal of Cancer, Vol.86, No.7, 1143-1149, 2002. (Summary) Phosphorothioate oligonucleotides and suramin bind to heparin binding proteins including DNA polymerases, and inhibit their functions. In the present study, we report inhibition of DNA-dependent protein kinase activity by phosphorothioate oligonucleotides, suramin and heparin. Inhibitory effect of phosphorothioate oligonucleotides on DNA-dependent protein kinase activity was increased with length and reached a plateau at 36-mer. The base composition of phosphorothioate oligonucleotides did not affect the inhibitory effect. The inhibitory effect by phosphorothioate oligodeoxycytidine 36-mer can be about 200-fold greater than that by the phosphodiester oligodeoxycytidine 36-mer. The inhibitory effect was also observed with purified DNA-dependent protein kinase, which suggests direct interaction between DNA-dependent protein kinase and phosphorothioate oligonucleotides. DNA-dependent protein kinase will have different binding positions for double-stranded DNA and phosphorothioate oligodeoxycytidine 36-mer because they were not competitive in DNA-dependent protein kinase activation. Suramin and heparin inhibited DNA-dependent protein kinase activity with IC(50) of 1.7 microM and 0.27 microg ml(-1) respectively. DNA-dependent protein kinase activities and DNA double-stranded breaks repair in cultured cells were significantly suppressed by the treatment with suramin in vivo. Our present observations suggest that suramin may possibly result in sensitisation of cells to ionising radiation by inactivation of DNA-dependent protein kinase and the impairment of double-stranded breaks repair. (Keyword) Antineoplastic Agents / Cell Culture Techniques / DNA Damage / DNA Repair / DNA-Activated Protein Kinase / DNA-Binding Proteins / Fibrinolytic Agents / Fibroblasts / Glioblastoma / Heparin / Humans / Nuclear Proteins / Oligonucleotides / Precursor Cell Lymphoblastic Leukemia-Lymphoma / Protein-Serine-Threonine Kinases / Radiation-Sensitizing Agents / Suramin / Thionucleotides / Tumor Cells, Cultured (Link to Publication Site) ● Publication site (DOI): 10.1038/sj.bjc.6600191 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11953863 ● Search Scopus @ Elsevier (PMID): 11953863 ● Search Scopus @ Elsevier (DOI): 10.1038/sj.bjc.6600191 (DOI: 10.1038/sj.bjc.6600191, PubMed: 11953863)
42.	A Enomoto, N Suzuki, C Liu, Y Kang, J Zhu, S Serizawa, Y Matsumoto, Akinori Morita, M Ito and Y Hosoi : Involvement of c-Jun NH2-terminal kinase-1 in heat-induced apoptotic cell death of human monoblastic leukaemia U937 cells., International Journal of Radiation Biology, Vol.77, No.8, 867-874, 2001. (Summary) Prolonged phosphorylation or activation of JNK1 was considered important for heat-induced apoptosis and JNK1 may control the process possibly through phosphorylation of HSP27 and caspase-9 activation in U937 cells. (Keyword) apoptosis / Base Sequence / Caspase 9 / Caspases / DNA Fragmentation / DNA Primers / Enzyme Activation / Enzyme Precursors / HSP27 Heat-Shock Proteins / Heat-Shock Proteins / Hot Temperature / Humans / Mitogen-Activated Protein Kinase 8 / Mitogen-Activated Protein Kinases / Mutation / Neoplasm Proteins / phosphorylation / U937 Cells (Link to Publication Site) ● Publication site (DOI): 10.1080/09553000110062512 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11571020 ● Search Scopus @ Elsevier (PMID): 11571020 ● Search Scopus @ Elsevier (DOI): 10.1080/09553000110062512 (DOI: 10.1080/09553000110062512, PubMed: 11571020)
43.	Akinori Morita, N Suzuki, Y Matsumoto, K Hirano, A Enomoto, J Zhu and K Sakai : p41 as a possible marker for cell death is generated by caspase cleavage of p42/SETbeta in irradiated MOLT-4 cells., Biochemical and Biophysical Research Communications, Vol.278, No.3, 627-632, 2000. (Summary) We have reported previously that X-irradiated MOLT-4 cells during their rapid cell death exhibited dose and time dependently a new protein named p41 detected by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). An antibody, AM-1, raised against partial peptide of p41 stained two spots, p41 and p42, unexpectedly. Amino acid sequence analysis of partial peptides showed homology between p41 and a putative oncogene, set. In the present study, N-terminal amino acid sequencing of p41 and p42, and polyclonal antibodies newly prepared against different partial peptide sequences revealed that p41 was a N-terminal truncation form of p42, and p42 was identified as SETbeta. The cleavage site was at carboxyl end of SNHD 18 of p42. Radiation-induced p42 cleavage as well as apoptotic cell death was suppressed by a caspase-specific inhibitor Ac-DEVD-CHO but not by Ac-YVAD-CHO. Further in vitro cleavage experiments with recombinant p42 and either irradiated cell extracts or recombinant caspases concluded that the cleavage of p42 into p41 was catalyzed by caspase(s) mainly by caspase-7. One of newly raised antibodies, AM-4, specific to p41 or specific to cleavage site of p42, was found useful enabling simple detection of p41 by 1-D PAGE instead of laborious 2-D PAGE. p41 may serve as a marker of apoptotic cell death. (Keyword) Amino Acid Sequence / apoptosis / Caspases / cell death / Cell Survival / Chromosomal Proteins, Non-Histone / Cloning, Molecular / Cysteine Proteinase Inhibitors / Histone Chaperones / Humans / Molecular Sequence Data / Oligopeptides / Peptide Fragments / Proteins / Radiation Tolerance / Recombinant Proteins / Transcription Factors / Tumor Cells, Cultured / X-Rays (Link to Publication Site) ● Publication site (DOI): 10.1006/bbrc.2000.3860 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 11095960 ● Search Scopus @ Elsevier (PMID): 11095960 ● Search Scopus @ Elsevier (DOI): 10.1006/bbrc.2000.3860 (DOI: 10.1006/bbrc.2000.3860, PubMed: 11095960)
44.	A Enomoto, N Suzuki, K Hirano, Y Matsumoto, Akinori Morita, K Sakai and H Koyama : Involvement of SAPK/JNK pathway in X-ray-induced rapid cell death of human T-cell leukemia cell line MOLT-4., Cancer Letters, Vol.155, No.2, 137-144, 2000. (Summary) We found that SAPK/JNK was phosphorylated during X-ray-induced rapid cell death of MOLT-4 cells and that acid Sphingomyelinase inhibitor D609 suppressed the rapid cell death as well as phosphorylation of SAPK/JNK. Also C2-ceramide caused phosphorylation of SAPK/JNK, followed by rapid cell death. Further we isolated X-ray-resistant radiation-hybrid clones from MOLT-4 and 50 Gy irradiated mouse FM3A cells by repeated selections with 3 Gy irradiation. One of them named Rh-1a was found resistant to X-ray- as well as C2-ceramide-induced rapid cell death. Rh-1a cells had mouse DNA but no increase in either mouse or human Bcl-2 determined by Western blotting. Accumulation of p53 after X-irradiation was similarly observed in both parental MOLT-4 and Rh-1a cells. However, contrasting to prolonged and prominent phosphorylated status of SAPK/JNK in MOLT-4 cells, Rh-1a cells exhibited short transient increase and FM3A cells showed no increase of phosphorylated status SAPK/JNK after X-irradiation. Therefore, SAPK/JNK activation is considered important in X-ray-induced rapid cell death or apoptosis of MOLT-4 cells. (Keyword) Animals / Blotting, Southern / Blotting, Western / Bridged Compounds / Cell Death / Cell Line / Dose-Response Relationship, Radiation / Enzyme Inhibitors / Humans / Leukemia, T-Cell / Mice / Mitogen-Activated Protein Kinase 8 / Mitogen-Activated Protein Kinases / Phosphodiesterase Inhibitors / phosphorylation / Proto-Oncogene Proteins c-bcl-2 / signal transduction / Sphingomyelin Phosphodiesterase / Sphingosine / Thiones / Time Factors / Transfection / Tumor Cells, Cultured / Tumor Suppressor Protein p53 / X-Rays (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10822128 ● Search Scopus @ Elsevier (PMID): 10822128 (PubMed: 10822128)
45.	Y Matsumoto, N Suzuki, N Namba, N Umeda, J X Ma, Akinori Morita, M Tomita, A Enomoto, S Serizawa, K Hirano, K Sakaia, H Yasuda and Y Hosoi : Cleavage and phosphorylation of XRCC4 protein induced by X-irradiation., FEBS Letters, Vol.478, No.1-2, 67-71, 2000. (Summary) We report the p35 and p60 forms of XRCC4 protein, appearing in human leukemia MOLT-4 or U937 cells following X-irradiation or hyperthermia. p35 appeared in conjunction with the cleavage of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and the fragmentation of internucleosomal DNA, and was suppressed by Ac-DEVD-CHO. p35 was also produced in vitro by treating MOLT-4 cell lysate with recombinant caspases, suggesting that p35 was a caspase-cleaved fragment of XRCC4 in apoptotic cell death. p60 was sensitive to treatment with phosphatase or wortmannin and was undetectable in M059J cells deficient in DNA-PKcs. However, p60 was found in ataxia-telangiectasia cells after irradiation. These results indicated p60 as a phosphorylated form of XRCC4, requiring DNA-PKcs but not ataxia-telangiectasia mutated (ATM). (Keyword) Androstadienes / Blotting, Western / Caspase 3 / Caspase 7 / Caspase Inhibitors / Caspases / Cell Cycle Proteins / DNA-Activated Protein Kinase / DNA-Binding Proteins / Hot Temperature / Humans / molecular weight / Nuclear Proteins / Peptide Fragments / Phosphatidylinositol 3-Kinases / phosphorylation / Protein-Serine-Threonine Kinases / Recombinant Proteins / Tumor Cells, Cultured / Tumor Suppressor Proteins / U937 Cells (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10922471 ● Search Scopus @ Elsevier (PMID): 10922471 (PubMed: 10922471)
46.	Y Kang, K Hirano, N Suzuki, A Enomoto, Akinori Morita, T Irimura and K Sakai : Increased expression after X-irradiation of MUC1 in cultured human colon carcinoma HT-29 cells., Gann : Japanese Journal of Cancer Research, Vol.91, No.3, 324-330, 2000. (Summary) The effect of X-irradiation on production of MUC1 was studied with human colon carcinoma HT-29 cells. As evaluated by immunocytochemical staining, the percentages of MUC1-positive cells in cells at 4 days after 6 Gy irradiation and in unirradiated control cells were 52 +/- 3.5% (n = 6) and 26 +/- 2.8% (n = 6), respectively. Flow-cytometric analysis of living cells showed that MUC1 began to rise from day 1, reaching a plateau by day 4 after 6 Gy irradiation. Western blot analysis with monoclonal antibody MY.1E12 against glycosylated MUC1 (mature form) showed dose-dependent increases of two bands (500 and 390 kDa) corresponding to two polymorphic MUC1 alleles. Premature forms of MUC1 (350 and 240 kDa) were detectable with monoclonal antibody HMFG-2 only in irradiated cells, suggesting that new core protein synthesis had been induced. The transcriptional activity of the MUC1 gene was analyzed in terms of transient expression of MUC1-CAT reporter plasmids containing 5'-flanking sequences of the MUC1 gene fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The results of CAT assay indicate that enhanced expression of MUC1 in irradiated HT-29 cells was due to upregulation of MUC1 transcription, and required the upstream promoter. (Keyword) Antibodies, Monoclonal / Blotting, Western / Cell Survival / Chloramphenicol O-Acetyltransferase / Dose-Response Relationship, Radiation / Flow Cytometry / HT29 Cells / Humans / immunohistochemistry / Mucin-1 / Plasmids / Time Factors / Transcription, Genetic / Transfection / Up-Regulation (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 10760692 ● Search Scopus @ Elsevier (PMID): 10760692 (PubMed: 10760692)

Review, Commentary:

1.	Akinori Morita, Yuichi Nishiyama, Takuma Sakai and Yuichi Higashi : Molecular Mechanisms of Acute Radiation Intestinal Injury and Its Control, Radiation Environment and Medicine, Vol.13, No.1, 10-18, Feb. 2024. (Link to Publication Site) ● Publication site (DOI): 10.51083/radiatenvironmed.13.1_10 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390580936920512640 ● Search Scopus @ Elsevier (DOI): 10.51083/radiatenvironmed.13.1_10 (DOI: 10.51083/radiatenvironmed.13.1_10, CiNii: 1390580936920512640)
2.	Akinori Morita, Yuichi Nishiyama, Takuma Sakai and HIGASHI Yuichi : Molecular mechanisms of acute radiation intestinal injury and its control, 放射線生物研究 = Radiation biology research communications : 放射線生物研究会機関誌, Vol.58, No.2, 93-109, Jun. 2023. (Tokushima University Institutional Repository) ● Metadata: 118821 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050298588047514624 (Tokushima University Institutional Repository: 118821, CiNii: 1050298588047514624)
3.	Yuichi Nishiyama and Akinori Morita : Development of radioprotector based on the radiosensitivity modification by p53 regulation, Radiation Biology Research Communications, Vol.54, No.4, 237-250, Dec. 2019. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520009408701551744 (CiNii: 1520009408701551744)
4.	Shintaroh Ochi, Yuichi Nishiyama and Akinori Morita : Development of p53-targeting drugs that increase radioresistance in normal tissues., The Journal of Medical Investigation : JMI, Vol.66, No.3.4, 219-223, Aug. 2019. (Summary) Radiation damage to normal tissues is a serious concern in radiation therapy. Advances in radiotherapeutic technology have improved the dose distribution of the target volumes and risk organs, but damage to risk organs that are located within the irradiation field still limits the allowable prescription dose. To overcome this dose-limiting toxicity, and to further improve the efficacy of radiotherapy, the development of drugs that protect normal tissues but not cancer tissues from the effects of radiation are expected to be developed based on molecular target-based drugs. p53 is a well-known transcription factor that is closely associated with radiation-induced cell death. In radiation-injured tissues, p53 induces apoptosis in hematopoietic lineages, whereas it plays a radioprotective role in the gastrointestinal epithelium. These facts suggest that p53 inhibitor would be effective for radioprotection of the hematopoietic system, and that a drug that upregulates the radioprotective functions of p53 would enhance the radioresistance of gastrointestinal tissues. In this review, we summarize recent progress regarding the prevention of radiation injury by regulating p53 and provide new strategic insights into the development of radioprotectors in radiotherapy. J. Med. Invest. 66 : 219-223, August, 2019. (Tokushima University Institutional Repository) ● Metadata: 114026 (Link to Publication Site) ● Publication site (DOI): 10.2152/jmi.66.219 (Link to Search Site for Scientific Articles) ● PubMed @ National Institutes of Health, US National Library of Medicine (PMID): 31656277 ● Search Scopus @ Elsevier (PMID): 31656277 ● Search Scopus @ Elsevier (DOI): 10.2152/jmi.66.219 (Tokushima University Institutional Repository: 114026, DOI: 10.2152/jmi.66.219, PubMed: 31656277)
5.	Akinori Morita and Shohei Ujita : 正常組織の耐容線量を高める放射線防護剤の開発, Shikoku Acta Medica, Vol.73, No.5, 6, 249-256, Dec. 2017. (Summary) The progress of high-precision radiation therapy in recent years has been remarkable, and it has become possible to obtain a high therapeutic effect by improving dose concentration. However, in order to prevent adverse events from occurring in organs at risk, the risks of radiation injury in the normal tissues still determine the limits of the tolerable dose. Now, it is hoped that improvement of tolerable dose by a biological modification of radiation sensitivity using some molecular target drugs. Since nearly half of cancer patients have a mutation in the TP53 gene that encodes p53, p53 regulatory agents are expected to exert a selective protection of normal tissues in p53‐deficient cancer therapy. We proceeded with the exploration of 8‐quinolinol (8‐HQ) derivatives that target a zinc binding site within the p53 molecule, and found several radioprotectors controlling p53 activity. 5‐chloro‐8‐quinolinol (5CHQ), which is currently in focus, has a unique p53‐modulating activity that shifts its transactivation from proapoptotic to protective responses including enhancing p21 induction and suppressing PUMA induction. The dose-reduction factors of 5CHQ in total-body and abdominally irradiated mice were about 1.2 and 1.3, respectively. It is expected to create a new radioprotective agent that can be applied to cancer therapy. (Keyword) p53 / apoptosis / radioprotector (Tokushima University Institutional Repository) ● Metadata: 112047 (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1050001337467469312 (Tokushima University Institutional Repository: 112047, CiNii: 1050001337467469312)
6.	Akinori Morita and 大谷聡一郎 : 科学教養講座バナデート--アポトーシスを抑える新しいタイプの放射線防護剤, 理大科学フォーラム, Vol.27, No.12, 28-33, Dec. 2010. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520290883906302208 (CiNii: 1520290883906302208)
7.	田中薫, 王冰 and Akinori Morita : Vanadate : A Novel Type of Radioprotector Acts by Inhibiting p53-Mediated Apoptosis, 放射線科学, Vol.53, No.11, 15-19, Nov. 2010. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520010380298223744 (CiNii: 1520010380298223744)
8.	Akinori Morita, Shinichi YAMAMOTO, Masahiko IKEKITA, BING WANG and Kaoru TANAKA : Vanadate : A Novel Type of Radioprotector Acts by Inhibiting p53, Radioisotopes, Vol.59, No.7, 459-462, Jul. 2010. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1390001204156178816 (CiNii: 1390001204156178816)
9.	Akinori Morita, 鈴木紀夫 and 細井義夫 : アポトーシスシグナリングと放射線防護, Radiation Biology Research Communications, Vol.40, No.4, 360-384, Dec. 2005. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1520009408954323072 (CiNii: 1520009408954323072)

Proceeding of International Conference:

1.	Sonoyama Yuichiro, Yuichi Nishiyama, Akinori Morita, Wang Bing, Sawatani Megumi, Shimokawa Takashi and Aoki Shin : Protective effect of sodium orthovanadate against radiation-induced male infertility in mice, The 8th International Symposium of the Network-type Joint Usage/ Research Center for Radiation Disaster Medical Science, Nagasaki, Feb. 2024.
2.	Takuma Sakai, Akinori Morita, Akinori Kanai, Bing Wang, Atsushi Enomoto, Shohei Ujita, Shin Aoki, Hidetoshi Satoh, Ryoya Kawabata, Masahiro Sakaue, Yuichi Nishiyama and Toshiya Inaba : A comprehensive analysis of the effects of 5CHQ on the radiation-injured intestinal epithelium, The 4th International Symposium of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science, Hiroshima, Feb. 2020.
3.	Yuichi Nishiyama, Akinori Morita, Wang Bing, Tanaka Kaoru, Katsube Takanori, Murakami Masahiro, Ochi Shintaro, Teraoka Tatsuro, Dwindling Ramadhani, Shimokawa Takashi, Neon Mitsuru and Aoki Shin : Protective effects of p53-regulating agents against high-LET radiation-induced injury in mice., 2nd Technological Competency as Caring in the Health Sciences 2018, Tokushima, Aug. 2018.
4.	Shohei Ujita, Akinori Morita, Shin Aoki, Yurie Nishi, Tatsuro Teraoka, Megumi Sasatani, Bing Wang, Ippei Takahashi, Kaoru Tanaka, Tomoaki Yamakawa, Mitsuru Nenoi, Kenji Kamiya and Toshiya Inaba : Requirement of the 8-hydroxyl group in the 5-chloro-8-quinolinol for its action as a radioprotective agonist, The 1st International Symposium of the network-type Joint Usage/ Research Center for Radiation Disaster Medical Science, Hiroshima, Feb. 2017.
5.	Akinori Morita, Ippei Takahashi, Shin Aoki, Bing Wang, Shinya Ariyasu, Megumi Sasatani, Kaoru Tanaka, Tetsuji Yamaguchi, Keiji Tanimoto, Mitsuru Nenoi, Kenji Kamiya, Yasushi Nagata, Yoshio Hosoi and Toshiya Inaba : A chemical modulator of p53 transactivation that acts as a radioprotective agonist, 4th international postgraduate conference on pharmaceutical sciences (iPoPs 2016), Chiba, Feb. 2016.
6.	Akinori Morita, Ippei Takahashi, Shin Aoki, Bing Wang, Shinya Ariyasu, Megumi Sasatani, Kaoru Tanaka, Tetsuji Yamaguchi, Keiji Tanimoto, Kenji Kamiya, Yoshio Hosoi, Yasushi Nagata and Toshiya Inaba : KH-3, a novel chemical modulator of p53, enhances p21 induction and protects mice from gastrointestinal death by abdominal irradiation., 15th International Congress of Radiation Research, Kyoto, May 2015.
7.	Bing Wang, Kaoru Tanaka, Akinori Morita and Mitsuru Nenoi : A potent mitigator of radiation-induced damage to the hematopoietic system in mice, The 7th National Congress of Radiation Medicine and Protection and The 20th Anniversary Tournament of The Radiological Hygiene Commission, Chinese Society of Preventive Medicine, Chong Qing, China, Oct. 2014.
8.	Bing Wang, Kaoru Tanaka, Akinori Morita and Mitsuru Nenoi : A potent mitigator of radiation-induced damage to the hematopoietic system in mice, First China International Symposium of Protective Agents Against Injury Induced by Ionizing Radiation, Tianjin, China, Oct. 2014.
9.	Ippei Takahashi, Akinori Morita, Shin Aoki, Bing Wang, Megumi Sasatani, Shinya Ariyasu, Kamiya Kenji, Yoshio Hosoi, Yasushi Nagata and Toshiya Inaba : KH-3, A Transcriptional Modulator of p53, Protects Mice From Radiation-Induced Gastrointestinal Syndrome, 56th Annual Meeting of American Society for Radiation Oncology, San Francisco, Sep. 2014. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ijrobp.2014.05.2268 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijrobp.2014.05.2268 (DOI: 10.1016/j.ijrobp.2014.05.2268)
10.	Ippei Takahashi, Akinori Morita, Shin Aoki, Bing Wang, Yoshio Hosoi, Yuko Kaneyasu, Masahiro Kenjo, Tomoki Kimura, Yuji Murakami and Yasushi Nagata : The Mechanism of A Novel Radioprotector, 8-Quinolinol Derivative KH-3, 55th Annual Meeting of American Society for Radiation Oncology, Atlanta, Sep. 2013. (Link to Publication Site) ● Publication site (DOI): 10.1016/j.ijrobp.2013.06.1690 (Link to Search Site for Scientific Articles) ● Search Scopus @ Elsevier (DOI): 10.1016/j.ijrobp.2013.06.1690 (DOI: 10.1016/j.ijrobp.2013.06.1690)
11.	Yoshio Hosoi, Yuji Tanno, Akinori Morita and Keiji Tanimoto : Radiation sensitization though regulation of transcriptional factor Sp1., 14th International Congress of Radiation Research, Warsaw, Aug. 2011.
12.	Akinori Morita : Vanadate: a novel type of radioprotector acts by inhibiting both transcription-dependent and transcription-independent p53 apoptotic pathways., 5th TUS International Collaboration Workshop, Tokyo, Dec. 2010.
13.	Atsushi Enomoto, Akinori Morita, Naoki Kido, Michihiko Ito, Yoshio Hosoi and Kiyoshi Miyagawa : Negative regulation of MAPKKK in SAPK pathways by a novel protein kinase, 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress in conjunction with 79th Annual Meeting of the Japanese Biochemical Society and 29th Annual Meeting of the Molecular Biology Society of Japan, Kyoto, Jun. 2006.

Proceeding of Domestic Conference:

1.	Akinori Morita : 日本放射線腫瘍学会第14回放射線生物学セミナー「がん微小環境と放射線治療」 ~放射線細胞死の多様性とその制御~, 日本放射線腫瘍学会第14回放射線生物学セミナー, Mar. 2024.
2.	Akinori Morita : 急性放射線誘発消化管症候群の分子機構とその制御, 第24回菅原・大西記念癌治療増感シンポジウム, Feb. 2024.
3.	GHOSH Sharmila, Akinori Morita, Yuichi Nishiyama, HIGASHI Yuichi and YUICHIROH Sonoyama : Rectal epithelial stem cell kinetics in acute radiation enteritis, ⽇本放射線影響学会第66回⼤会, Nov. 2023.
4.	YUICHIROH Sonoyama, Yuichi Nishiyama, Akinori Morita, 王冰, 笹谷めぐみ, 下川卓志 and 青木伸 : Sodium orthovanadate protects male fertility against radiation exposure, ⽇本放射線影響学会第66回⼤会, Nov. 2023.
5.	Akinori Morita, TANIMOTO Taiga, HIGASHI Yuichi, Yuichi Nishiyama, SHOJI Tsugumi, 村田貴嗣, 小向杏佳, 金井昭教, Taisei Kunii, Takuma Sakai, Ryo Sadatomi, 王冰, 下川卓志, 中田健也, 武村直紀, Tatsuya Saitoh, 稲葉俊哉 and 椎名勇 : 炎症誘発性プラットフォームを標的とする放射線防護剤の開発, 第60回日本放射線腫瘍学会生物部会学術大会, Jun. 2023.
6.	Akinori Morita : 日本放射線腫瘍学会第13回放射線生物学セミナー「集学的がん治療における放射線生物学」 ~英文定義から学ぶ放射線細胞死~, 日本放射線腫瘍学会第13回放射線生物学セミナー, Feb. 2023.
7.	YUICHIROH Sonoyama, Yuichi Nishiyama, Akinori Morita, 王冰, 佐藤秀哉 and 青木伸 : p53制御剤による放射線被ばくに対する雄性妊孕性温存, 第59回日本放射線腫瘍学会生物部会学術大会, Jun. 2022.
8.	Taiga Tanimoto, Akinori Morita, Yuichi Nishiyama, Takatsugu Murata, Anjyu Sakai, Akinori Kanai, Yuichi Higashi, Taisei Kunii, Takuma Sakai, Ryo Sadatomi, Bing Wang, Takashi Shimokawa, Kenya Nakata, Naoki Takemura, Tatsuya Saitoh, Toshiya Inaba and Isamu Shiina : A novel immunomodulatory compound that prevents sub-total body irradiation-induced intestinal death, The 64th Annual Meeting of the Japan Radiation Research Society, Sep. 2021.
9.	HIGASHI Yuichi, Akinori Morita, Yuichi Nishiyama, 村田貴嗣, 酒井杏樹, 金井昭教, TANIMOTO Taiga, Takuma Sakai, 中田健也, 武村直紀, Tatsuya Saitoh, 稲葉俊哉 and 椎名勇 : 抗炎症作用を有する新規化合物の腸炎制御剤としての活性評価, 第29回日本Cell Death学会学術集会, Jul. 2021.
10.	Akinori Morita, 王冰, 田中薫, 勝部孝則, 村上正弘, 下川卓志, Yuichi Nishiyama, Shintaroh Ochi, 佐藤秀哉, 根井充 and 青木伸 : p53を標的とした放射線防護剤の粒子線治療における役割, 第58回生物部会学術大会・第49回放射線による制癌シンポジウム, Jun. 2021.
11.	TANIMOTO Taiga, Akinori Morita, Yuichi Nishiyama, 村田貴嗣, 酒井杏樹, 金井昭教, HIGASHI Yuichi, Shintaroh Ochi, Taisei Kunii, Takuma Sakai, Ryo Sadatomi, 王冰, 下川卓志, 中田健也, Tatsuya Saitoh, 稲葉俊哉 and 椎名勇 : 抗炎症作用を有する新規化合物の放射線防護剤としての活性評価, 第58回生物部会学術大会・第49回放射線による制癌シンポジウム, Jun. 2021.
12.	Akinori Morita, Tatsuta Shogo, Sakaue Masahiro, Fujita Ria, Hanaya Kengo, Sugai Takeshi, Yuichi Nishiyama, Ochi Shintaro, Sakai Takuma, Wang Bing and Aoki Shin : Evaluation of the radioprotective effects of flavonoids., The 62th Annual Meeting of the Japan Radiation Research Society, Nov. 2019.
13.	Yuichi Nishiyama, Akinori Morita, Wang Bing, Sakai Takuma, Ramadhani Dwi, Satoh Hidetoshi, Kawabata Ryoya, Tanaka Kaoru, Sasatani Megumi, Ochi Shintaro, Nenoi Mitsuru and Aoki Shin : The p53 inhibitor sodium orthovanadate is not effective in relieving acute gastrointestinal syndrome of subtotal-body irradiated mice., The 62th Annual Meeting of the Japan Radiation Research Society, Nov. 2019.
14.	Sakai Takuma, Akinori Morita, Kanai Akinori, Wang Bing, Enomoto Atsushi, Ujita Shohei, Aoki Shin, Sato HIdetoshi, Kawabata Junya, Sakaue Masahito, Yuichi Nishiyama and Inaba Toshiya : The radioprotector 5CHQ upregulates gene expression of radioprotective humoral factors in acute radiation-injured murine intestinal epithelium., The 62th Annual Meeting of the Japan Radiation Research Society, Nov. 2019.
15.	Ochi Shintaro, Satoh Hidetoshi, Ujita Shohei, Tada kasumi, Yosuke Matsushita, MiIzuno Kosuke, Deguchi Yuichi, Suzuki Keiji, Tanaka Yoshimasa, Ueda Hiroshi, Inaba Toshiya, Hosoi Yoshio, Aoki Shin and Akinori Morita : Mechanism of action of p53-regulating anti-cell death compound discovered by chemical library screening., The 62th Annual Meeting of the Japan Radiation Research Society, Nov. 2019.
16.	Akinori Morita, 王冰, 田中薫, 勝部孝則, 村上正弘, Yuichi Nishiyama, Shintaroh Ochi, 寺岡達朗, 佐藤秀哉, 川端凌矢, 下川卓志, 根井充 and 青木伸 : p53制御による重粒子放射線防護効果, 第57回日本放射線腫瘍学会生物部会学術大会, Jun. 2019.
17.	Takuma Sakai, Yuichi Nishiyama, Akinori Morita, 王冰, ラマダニードゥウィー, 佐藤秀哉, 川端凌矢, 田中薫, 笹谷めぐみ, Shintaroh Ochi, 根井充 and 青木伸 : p53阻害剤バナデートは亜全身照射後のマウス腸管障害を促進する, 第57回日本放射線腫瘍学会生物部会学術大会,弘前, Jun. 2019.
18.	佐藤秀哉, Shintaroh Ochi, 水野皓介, Yosuke Matsushita, 出口雄一, 鈴木啓司, 田中義正, 植田弘師, 稲葉俊哉, 細井義夫, Akinori Morita and 青木伸 : 放射線防護活性を有する 2-Oxopyrrole 類の設計・合成及び活性評価, 日本薬学会第139年回, Mar. 2019.
19.	Shintaroh Ochi, 佐藤秀哉, Shohei Ujita, Kasumi Tada, Yosuke Matsushita, 水野皓介, 出口雄一, 鈴木啓司, 田中義正, 植田弘師, 稲葉俊哉, 細井義夫, 青木伸 and Akinori Morita : 化合物ライブラリーから選抜されたp53依存性細胞死抑制剤の作用機構解析, 日本放射線影響学会第61回大会, Nov. 2018.
20.	Takuma Sakai, Shohei Ujita, 榎本敦, Yohsuke Kawate, Yuichi Nishiyama, 寺岡達朗, 青木伸, 王冰, 金井昭教, 稲葉俊哉 and Akinori Morita : 放射線防護剤5CHQの遺伝子発現調節作用の網羅的解析, 日本放射線影響学会第61回大会, Nov. 2018.
21.	Yuichi Nishiyama, Taisei Kunii, 笹谷めぐみ, 寺岡達朗, Takuma Sakai, Yuichi Nishiyama, 神谷研二, 王冰, 青木伸 and Akinori Morita : p53調節剤5CHQの類縁体探索から見出された5QXの放射線防護活性評価, 日本放射線影響学会第61回大会, Nov. 2018.
22.	Akinori Morita, 王冰, 田中薫, 勝部孝則, 村上正弘, Yuichi Nishiyama, Shintaroh Ochi, 寺岡達朗, ラマダニードゥウィー, 下川卓志, 根井充 and 青木伸 : p53制御剤による重粒子放射線防護効果, 日本放射線影響学会第61回大会, Nov. 2018.
23.	佐藤秀哉, Shintaroh Ochi, 水野皓介, Yosuke Matsushita, 出口雄一, 鈴木啓司, 田中義正, 植田弘師, 稲葉俊哉, 細井義夫, Akinori Morita and 青木伸 : 2—oxopyrrole 骨格を有する放射線防護剤の設計・合成及び活性評, 第62回日本薬学会関東支部大会, Sep. 2018.
24.	Akinori Morita, 王冰, 田中薫, 勝部孝則, 村上正弘, ラマダニードゥウィー, 下川卓志, 根井充, Shintaroh Ochi, Yuichi Nishiyama, 寺岡達朗 and 青木伸 : 細胞死制御剤による重粒子放射線防護効果, 第56回日本放射線腫瘍学会生物部会学術大会, Jul. 2018.
25.	Akinori Morita, 王冰, 新井ひろみ, 田中薫, 勝部孝則, 村上正弘, ラマダニードゥウィー, 下川卓志, 根井充 and Shintaroh Ochi : Study of heavy ion beam protective effect by cell death regulator at individual mouse level, H29年度HIMAC共同利用研究成果発表会, Apr. 2018.
26.	氏田将平, 榎本敦, 川手耀介, 寺岡達朗, 青木伸 and Akinori Morita : 放射線防護剤5-chloro-8-quinolinolによる照射後のp53標的遺伝子発現変化の網羅的解析, 第256回徳島医学会学術集会, Feb. 2018.
27.	Shintaroh Ochi, Shohei Ujita, Kasumi Tada, Yosuke Matsushita, 水野皓介, 佐藤秀哉, 青木伸, 出口雄一, 鈴木啓司, 田中義正, 植田弘師, 稲葉俊哉, 細井義夫 and Akinori Morita : ケミカルライブラリーから選抜されたp53制御性放射線防護剤の作用機構解析, 日本放射線影響学会第60回大会, Oct. 2017.
28.	Shohei Ujita, 榎本敦 and Akinori Morita : 放射線防護剤5CHQによる照射後の遺伝子発現変化の網羅的解析, 日本放射線影響学会第60回大会, Oct. 2017.
29.	Tomoaki Yamakawa, 寺岡達朗, Akinori Morita, Shohei Ujita and 青木伸 : 5-クロロ-8-キノリノール誘導体の放射線防護活性評価, 日本放射線影響学会第60回大会, Oct. 2017.
30.	Akinori Morita, Shinsuke Shigematsu, Yusuke Hata, Yuko Yokogawa, Nanami Umetani, 太田のぞみ, 芝田夏実, Shohei Ujita, Tomoaki Yamakawa, 中田健也 and 椎名勇 : タモキシフェン類縁体リダイフェン-C，-Fは放射線損傷後のDNA修復過程を促進する, 日本放射線影響学会第60回大会, Oct. 2017.
31.	青木伸, 寺岡達朗, 西友里恵, 佐藤秀哉, 水野皓介, 嵯峨裕, Shohei Ujita, Tomoaki Yamakawa, Shintaroh Ochi, 大和田勇人, 王冰 and Akinori Morita : 亜鉛酵素研究・機械学習・ランダムスクリーニングに基づくp53制御性放射線防護剤の設計・合成・活性評価, 第35回メディシナルケミストリーシンポジウム, Oct. 2017.
32.	寺岡達朗, 西友里恵, 大和田勇人, Akinori Morita, Shohei Ujita, Tomoaki Yamakawa and 青木伸 : キノリノール骨格を持った放射線防護剤の設計，合成および活性評価, 第61回日本薬学会関東支部大会, Sep. 2017.
33.	Akinori Morita : 正常組織の耐容線量を高める放射線防護剤の開発(教授就任記念講演), 第255回徳島医学会学術集会, Aug. 2017.
34.	Akinori Morita : 医療応用を目指した正常組織の放射線防護, 第58回原子爆弾後障害研究会, Jun. 2017.
35.	勝部孝則, 田中薫, 王冰, 二宮康晴, Vares Guillaume, 川越大輝, 塩見尚子, 久保田善久, 劉強, Akinori Morita, 中島徹夫 and 根井充 : マウス脾細胞染色体異常における身体拘束ストレスによる放射線影響の修飾, 日本放射線影響学会第59回大会, Oct. 2016.
36.	Shinsuke Shigematsu, Akinori Morita, 秦佑輔, 横川裕子, 梅谷七海, 太田のぞみ, 芝田夏実, 氏田将平, 中田健也 and 椎名勇 : タモキシフェン類縁体リダイフェンの放射線防護機構解析, 日本放射線影響学会第59回大会, Oct. 2016.
37.	Akinori Morita, 高橋一平, 笹谷めぐみ, 青木伸, 王冰, 有安真也, 田中薫, 山口哲司, 谷本圭司, 根井充, 神谷研二, 永田靖, 細井義夫 and 稲葉俊哉 : p53 標的創薬による放射線防護, 日本放射線影響学会第59回大会, Oct. 2016.
38.	Shohei Ujita, Akinori Morita, 青木伸, 西友里恵, 寺岡達郎, 王冰, 笹谷めぐみ, 田中薫, 山川知晃, 根井充, 神谷研二 and 稲葉俊哉 : p53 を標的とする放射線防護剤5-chloro-8-quinolinol の作用機構解析, 日本放射線影響学会第59回大会, Oct. 2016.
39.	Akinori Morita, 高橋一平, 笹谷めぐみ, 青木伸, 王冰, 有安真也, 田中薫, 澤晶子, 西友里恵, 寺岡達郎, 氏田将平, 谷本圭司, 根井充, 神谷研二, 永田靖, 細井義夫 and 稲葉俊哉 : p53標的創薬研究から得られたp53転写調節剤5-クロロ-8-キノリノールの放射線防護作用機構解析, 日本Cell Death学会, Sep. 2016.
40.	青木伸, Akinori Morita, 王冰, 有安真也, 西友里恵, 寺岡達朗, Shohei Ujita, Daichi Fukui, 田中薫 and 田中智博 : がん放射線治療の副作用低減を目的とするp53標的放射線防護剤の開発, 第9回バイオ関連化学シンポジウム, Sep. 2015.
41.	Akinori Morita : Development of new radioprotectors that target p53, 平成26年度環境省・健康調査事業「屋外活動を制限された子供の放射線感受性変化に関する動物モデル研究」に係る講演会(放医研不定期講演会), Feb. 2015.
42.	勝部孝則, 田中薫, 王冰, 二宮康靖, Guillaume Vares, 劉強, Akinori Morita, 中島徹夫 and 根井充 : FISH法による身体拘束ストレスの放射線感受性修飾作用に関する解析, 日本放射線影響学会第57回大会, Oct. 2014.
43.	Bing Wang, Kaoru Tanaka, Takanori Katsube, Yasuharu Ninomiya, Guillaume Vares, Qiang Liu, Akinori Morita, Tetsuo Nakajima and Mitsuru Nenoi : Effects from Total Body X-Irradiation and Psychological Stress on the Hematopoietic System in Mice, 日本放射線影響学会第57回大会, Oct. 2014.
44.	横川裕子, Akinori Morita, 秦佑輔, 植竹祥子, 水澤彰人, 中田健也 and 椎名勇 : タモキシフェン類縁体リダイフェンの細胞死抑制効果の検討, 日本放射線影響学会第57回大会, Oct. 2014.
45.	秦佑輔, Akinori Morita, 横川裕子, 植竹祥子, 水澤彰人, 中田健也 and 椎名勇 : タモキシフェン類縁体リダイフェンの放射線防護効果と細胞毒性の検討, 日本放射線影響学会第57回大会, Oct. 2014.
46.	小野田貴祥, Akinori Morita, 浅沼哲雄, 有安真也, 澤晶子, 王冰, 田中薫, 根井充 and 青木伸 : 新規放射線防護剤候補化合物の活性評価, 日本放射線影響学会第57回大会, Oct. 2014.
47.	浅沼哲雄, Akinori Morita, 小野田貴祥, 有安真也, 王冰, 澤晶子, 田中薫, 高橋一平, 根井充, 稲葉俊哉 and 青木伸 : 8-キノリノール誘導体AS-2のp53依存性アポトーシス抑制機構, 日本放射線影響学会第57回大会, Oct. 2014.
48.	Akinori Morita, 高橋一平, 青木伸, 王冰, 有安真也, 笹谷めぐみ, 田中薫, 谷本圭司, 神谷研二, 細井義夫, 永田靖 and 稲葉俊哉 : 新規アポトーシス抑制剤KH-3の放射線防護活性評価, 日本放射線影響学会第57回大会, Oct. 2014.
49.	Akinori Morita : p53を標的とする新規放射線防護剤の開発, 医療機器安全管理研修会, Feb. 2014.
50.	Akinori Morita : Controlling acute radiation syndrome by regulating p53, 平成25年度環境省・健康調査事業「屋外活動を制限された子供の放射線感受性変化に関する動物モデル研究」に係る講演会(放医研不定期講演会), Feb. 2014.
51.	Shin Aoki, Shinya Ariyasu, Akinori Morita, Akiko Sawa, Ippei Takahashi, Bing Wang, Misato Hoshi, Takatoshi Uchida, Soichiro Ohya and Yoshio Hosoi : Design and Synthesis of Drugs that Reduce Side Effect of Radiotherapy, 第31回メディシナルケミストリーシンポジウム, Nov. 2013.
52.	Akinori Morita, Tomoki Murakami, Takeshi Morinaga, Keiji Tanimoto and Yoshio Hosoi : Requirement of mitochondria for ATM activation by extranuclear oxidative stress in cultured human hepatoblastoma cell line Hep G2 cells, 日本放射線影響学会第56回大会, Oct. 2013.
53.	高橋一平, Akinori Morita, 青木伸, 花屋賢悟, 有安真也, 王冰, 田中薫, 笹谷めぐみ, 谷本圭司, 細井義夫, 永田靖 and 稲葉俊哉 : 新規アポトーシス抑制剤KH-3の作用機構解析, 日本放射線影響学会第56回大会, Oct. 2013.
54.	Shinya Ariyasu, Akinori Morita, Ippei Takahashi, Bing Wang, Akiko Sawa, Misato Hoshi, Takatoshi Uchida, Soichiro Ohya, Yoshio Hosoi and Shin Aoki : p53を標的とする放射線防護剤の設計と合成, 第7回バイオ関連化学シンボジウム, Sep. 2013.
55.	細井義夫, Akinori Morita, 谷本圭司, 上原芳彦 and 村田泰彦 : 活性酸素によるATMの核外での活性化, 第51回日本放射線腫瘍学会生物部会学術大会, Jul. 2013.
56.	有安真也, Akinori Morita, 高橋一平, 澤晶子, 葛岡朋代, 内田孝俊, 大谷聡一郎, 細井義夫 and 青木伸 : p53を標的とする放射線防護剤の探索と機構解析, 日本化学会第93春季年回, Mar. 2013.
57.	羽鳥麻奈美, 山本卓, 友光裕子, 椎名勇, 梅田絵梨, 戸田年総, 大篭友博, 岩本真知子, Akinori Morita, 渡邊千尋, 植竹祥子, 矢守隆夫, 吉見陽児, 四宮貴久 and 池北雅彦 : 新規細胞死誘導剤リダイフェンGの作用機構の解析並びに標的分子の同定, 第85回日本生化学会大会, Dec. 2012.
58.	内田知紗, 望月万里, 吉見陽児, Akinori Morita, 羽染芳宗, 井田紀子, 船津修, 菅原二三男 and 池北雅彦 : 新規抗癌剤候補化合物DDTCT誘導性細胞増殖抑制に関連する遺伝子の解析, 第85回日本生化学会大会, Dec. 2012.
59.	北川純子, 吉見陽児, 望月万里, Akinori Morita, 菅原二三男 and 池北雅彦 : カバノアナタケから同定された抗癌剤候補化合物DDTCTの作用機構解析, 第85回日本生化学会大会, Dec. 2012.
60.	葛岡朋代, Akinori Morita, 大谷聡一郎, 花屋賢悟, 有安真也, 高橋一平, 王冰, 池北雅彦, 細井義夫 and 青木伸 : 一時的にp53を選択的に阻害する放射線防護剤の設計及び合成, 第56回日本薬学会関東支部大会, Oct. 2012.
61.	高橋一平, Akinori Morita, 花屋賢悟, 内田孝俊, 王冰, 田中薫, 池北雅彦, 永田靖, 青木伸 and 細井義夫 : p53に作用する8‐キノリノール誘導体KH‐3の作用機構解析, 日本放射線影響学会第55回大会, Sep. 2012.
62.	Akinori Morita, 花屋賢悟, 大谷聡一郎, 高橋一平, 王冰, 田中薫, 池北雅彦, 永田靖, 青木伸 and 細井義夫 : p53を標的とする新規放射線防護剤の開発, 日本放射線影響学会第55回大会, Sep. 2012.
63.	Akinori Morita, 内田孝俊, 大谷聡一郎, 花屋賢悟, 王冰, 田中薫, 細井義夫, 青木伸 and 池北雅彦 : p53転写非依存性アポトーシス誘導経路に作用する8-キノリノール誘導体 KH-13 の作用機構解析, 第50回日本放射線腫瘍学会生物部会学術大会, Jun. 2012.
64.	花屋賢悟, 内田孝俊, Akinori Morita, 大谷聡一郎, 葛岡朋代, 有安真也, 王冰, 田中薫, 細井義夫, 池北雅彦 and 青木伸 : p53の亜鉛イオンをターゲットとする放射線防護剤とそのプロドラッグの開発, 日本薬学会第132年会, Mar. 2012.
65.	Akinori Morita : 放射線の基礎知識と対策について, 平成23年度第5ブロック赤十字救急法等指導員研修会(日本赤十字社広島県支部), Feb. 2012.
66.	谷本圭司, 中村秀明, 河本健, 加藤幸夫, 檜山英三, 檜山桂子, 西山正彦, Akinori Morita and 細井義夫 : DNA修復関連遺伝子の低酸素応答性転写抑制機構, 日本放射線影響学会第54回大会, Nov. 2011.
67.	Akinori Morita, 佐藤元俊, 谷本圭司 and 細井義夫 : 過酸化水素・放射線によるATMを介したp53 Ser‐15のリン酸化とアポトーシス, 日本放射線影響学会第54回大会, Nov. 2011.
68.	内田孝俊, Akinori Morita, 大谷聡一郎, 花屋堅悟, WANG Bing, 田中薫, 細井義夫, 青木伸 and 池北雅彦 : p53転写非依存性アポトーシス経路に特異的に作用する亜鉛キレート化剤の作用機構解析, 日本放射線影響学会第54回大会, Nov. 2011.
69.	大谷聡一郎, Akinori Morita, MOHD Zulkefeli, 伊石安里, 王冰, 田中薫, 岡崎遥奈, 吉野美那子, 細井義夫, 青木伸 and 池北雅彦 : p53分子内の亜鉛イオン結合部位を標的とする新規放射線防護剤の開発, 日本放射線影響学会第54回大会, Nov. 2011.
70.	吉野美那子, Akinori Morita, 小林新緑, 高畠香織, 細井義夫 and 池北雅彦 : ゼオシンベクターを用いた放射線感受性遺伝子新規探索法の開発, 日本放射線影響学会第54回大会, Nov. 2011.
71.	羽鳥麻奈美, Akinori Morita, 椎名勇, 中田健也, 戸崎雄太, WANG Yanwen, 戸田年総, 大篭友博, 矢守隆夫, 吉見陽児 and 池北雅彦 : 新規細胞死誘導剤リダイフェン‐Gの薬物標的分子の同定, 第84回日本生化学会大会合同大会, Sep. 2011.
72.	七尾友久, 大篭友博, Akinori Morita, 吉見陽児, 船津修 and 池北雅彦 : 細胞接着分子ICAM‐5のAsn54に結合するN‐型糖鎖の機能解析, 第84回日本生化学会大会合同大会, Sep. 2011.
73.	横山翔, 袴田真矢, Akinori Morita, 沓村憲樹, 齋藤隆夫 and 池北雅彦 : 新規アポトーシス誘導剤RK96の作用機構の解明, 第84回日本生化学会大会合同大会, Sep. 2011.
74.	北川純子, 望月万里, Akinori Morita, 村田寛, 菅原二三男 and 池北雅彦 : カバノアナタケから同定された抗癌剤候補化合物DDTCTの作用機構解析, 第84回日本生化学会大会合同大会, Sep. 2011.
75.	池田玲子, 黒澤正樹, 岡林賞純, 武江彩子, 吉原正道, 坂井教郎, 船津修, Akinori Morita, 池北雅彦 and 小中原猛雄 : 3‐(3‐フェノキシベンジル)アミノ‐β‐カルボリン:α‐チューブリンを目標にした新しい抗腫瘍薬, 第5回バイオ関連化学シンポジウム, Sep. 2011.
76.	Akinori Morita, 大谷聡一郎, 青木伸, ZULKEFELI Mohd, 板倉寿成, 吉野美那子, 池北雅彦 and 細井義夫 : p53分子内の亜鉛イオン結合部位を標的とする新規放射線防護剤の開発, 第36回中国地区放射線影響研究会, Jul. 2011.
77.	Akinori Morita : p53分子内の亜鉛イオン結合部位を標的とする新規放射線防護剤の開発, 第107回原医研セミナー, Jul. 2011.
78.	細井義夫, Akinori Morita and 谷本圭司 : 過酸化水素によるATMを介したp53 Ser-15のリン酸化, 第17回国際癌治療増感研究会, Jun. 2011.
79.	杉村尚則, 沓村憲樹, Akinori Morita, 池北雅彦 and 齊藤隆夫 : 新規アポトーシス物質探索を指向した新規ベンゾチアジアジン誘導体の合成, 日本化学会第91春季年会, Mar. 2011.
80.	七尾友久, 大篭友博, Akinori Morita, 船津修 and 池北雅彦 : 終脳特異的に発現する細胞接着分子ICAM-5に結合したN-型糖鎖の機能, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
81.	北川純子, 望月万里, Akinori Morita, 羽染芳宗, 井田紀子, 村田寛, 船津修, 菅原二三男 and 池北雅彦 : カバノアナタケから同定された抗癌剤候補化合物DDTCTの作用機構解析, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
82.	羽鳥麻奈美, Akinori Morita, 椎名勇, 中田健也, 戸崎雄太, 王エンブン, 戸田年総, 大篭友博, 矢守隆夫 and 池北雅彦 : 新規アポトーシス誘導剤リダイフェン-Gの薬物標的分子の同定, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
83.	堤知彦, 池田聖樹, 雪澤俊輔, Akinori Morita, 倉持幸司, 船津修, 小林進 and 池北雅彦 : エポラクタエン1bとその標的分子Peroxiredoxin 1によるアポトーシス誘導機構の解析, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
84.	船津修, 三ッ廣香里, Akinori Morita and 池北雅彦 : ラミニンはラット膵臓導管由来ARIP細胞のインスリン産生細胞への分化を誘導する, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
85.	横山翔, 袴田真矢, Akinori Morita, 沓村憲樹, 齋藤隆夫 and 池北雅彦 : 新規アポトーシス誘導剤RK96の作用機構の解明, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
86.	小林倫巳, 鈴木康太郎, 中野薫, Akinori Morita, 船津修 and 池北雅彦 : アクチビン Aによるヒト神経芽細胞腫のSMAD非依存的な神経分化・生存機構の解析, 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会, Dec. 2010.
87.	王冰, 田中薫, Akinori Morita, 尚奕, VARES Guillaume, 森本泰子, 藤田和子 and 根井充 : オルトバナジン酸ナトリウム(バナデート)は，マウスにおいて全身照射後の障害に対して有効な緩和剤(Mitigator) である, 日本放射線影響学会第53回大会, Oct. 2010.
88.	内田孝俊, Akinori Morita, 大谷聡一郎, 青木伸, 花屋賢悟, 王冰, 田中薫, 岡崎遥奈, 池北雅彦 and 池北雅彦 : p53転写非依存性アポトーシス誘導経路に特異的に作用する亜鉛キレート化剤の作用機構解析, 日本放射線影響学会第53回大会, Oct. 2010.
89.	大谷聡一郎, Akinori Morita, 青木伸, モハマドズルキフリ, 板倉寿成, 王冰, 田中薫, 岡崎遥奈, 吉野美那子 and 池北雅彦 : p53分子内の亜鉛イオン結合部位を標的とする新規阻害剤の開発, 日本放射線影響学会第53回大会, Oct. 2010.
90.	Akinori Morita : 放射線誘発アポトーシスの分子機構とそれを利用した防護剤に関する研究, 日本放射線影響学会第53回大会, Oct. 2010.
91.	伊藤あずさ, Akinori Morita, 大谷聡一郎, 山元真一, 榎本敦, 池北雅彦 and 細井義夫 : タンパク質合成阻害剤シクロヘキシミドを用いたMOLT-4細胞におけるp53依存性放射線誘発アポトーシス経路の解析, 日本放射線影響学会第53回大会, Oct. 2010.
92.	Akinori Morita : バナデート: p53 転写依存性・非依存性両経路に作用する新しいタイプの放射線防護剤, 放医研研究会講演会, Jun. 2010.
93.	青木伸, 中村有香里, 塚本雅登, 高澤涼子, Akinori Morita, 北村正典, 田沼靖一 and 池北雅彦 : 亜鉛イオン(II)との錯体生成によって活性化されるアポトーシス誘導剤の設計と合成, 日本薬学会第130年会, Mar. 2010.
94.	Akinori Morita, 山元真一, 王冰, 田中薫, 伊藤あずさ, 榎本敦, 松本義久, 船津修, 細井義夫, 鈴木紀夫 and 池北雅彦 : オルトバナジン酸ナトリウムによるp53転写非依存性アポトーシス抑制機構および放射線防護効果, 日本放射線影響学会第52回大会, Nov. 2009.
95.	望月万里, Akinori Morita, 羽染芳宗, 井田紀子, 村田寛, 船津修, 菅原二三男 and 池北雅彦 : カバノアナタケから同定されたDDTCTの細胞増殖抑制効果, 第82回日本生化学会大会, Oct. 2009.
96.	七尾友久, 大篭友博, 船津修, Akinori Morita and 池北雅彦 : 終脳特異的に発現する細胞接着分子ICAM-5に結合したN-型糖鎖の機能, 第82回日本生化学会大会, Oct. 2009.
97.	安藤大之, 船津修, Akinori Morita and 池北雅彦 : ラット肝癌細胞dRLh-84のBrefeldin A耐性株における性状解析, 第82回日本生化学会大会, Oct. 2009.
98.	鈴木康太郎, 船津修, Akinori Morita and 池北雅彦 : Activin A で誘導されるヒト神経芽細胞腫の神経分化および生存活性メカニズムの解析, 第82回日本生化学会大会, Oct. 2009.
99.	大篭友博, 船津修, 中家修一, Akinori Morita and 池北雅彦 : 終脳特異的に発現する細胞接着分子ICAM-5に結合したN-型糖鎖の構造解析, 第34回日本医用マススペクトル学会年会, Sep. 2009.
100.	池北雅彦, 長坂美歩, 船津修, Akinori Morita, 福田覚 and 山本禎一 : 中枢神経細胞ならびに杯細胞に存在するシアリル化糖鎖構造を認識するモノクローナル抗体1C8の性状解析, バイオイメージング, Vol.18, No.2, 98-99, Jul. 2009. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1570854175875777280 (CiNii: 1570854175875777280)
101.	望月万里, Akinori Morita, 羽染芳宗, 井田紀子, 村田寛, 船津修, 菅原二三男 and 池北雅彦 : カバノアナタケから同定されたDDTCTの細胞増殖抑制効果, 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会, Dec. 2008.
102.	安藤大之, 船津修, Akinori Morita and 池北雅彦 : ラット肝癌細胞dRLh-84のBrefeldin A耐性株における性状解析, 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会, Dec. 2008.
103.	鈴木康太郎, 船津修, Akinori Morita and 池北雅彦 : Activin Aで誘導されるヒト神経芽細胞腫の神経分化および生存活性メカニズムの解析, 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会, Dec. 2008.
104.	長坂美歩, 船津修, 鈴木康太郎, Akinori Morita, 斉藤慎一 and 池北雅彦 : 合成低分子化合物sk8-78-hyd-2はヒト神経芽細胞腫SK-N-SHの神経突起伸長を増強する, 第31回日本分子生物学会年会・第81回日本生化学会大会合同大会, Dec. 2008.
105.	榎本敦, 木戸直樹, Akinori Morita, 細井義夫 and 宮川清 : STK38を介した新しいストレスシグナルネットワーク, 日本放射線影響学会第51回大会, Nov. 2008.
106.	Akinori Morita, 山元真一, 王冰, 田中薫, 伊藤あずさ, 榎本敦, 松本義久, 船津修, 細井義夫, 鈴木紀夫 and 池北雅彦 : オルトバナジン酸ナトリウムによるp53転写非依存性アポトーシス抑制機構, 日本放射線影響学会第51回大会, Nov. 2008.
107.	中永博章, Akinori Morita, 船津修 and 池北雅彦 : オリゴシアル酸を認識するモノクローナル抗体の作製及び抗体認識分子の同定, 第28回日本糖質学会, Aug. 2008.
108.	大篭友博, 船津修, 中家修一, Akinori Morita and 池北雅彦 : 終脳特異的に発現する細胞接着分子テレンセファリンに結合したN-型糖鎖の構造解析, 第28回日本糖質学会, Aug. 2008.
109.	榎本敦, 木戸直樹, Akinori Morita, 細井義夫 and 宮川清 : STK38によるストレスシグナル制御, 第17回日本アポトーシス研究会学術集会, Aug. 2008.
110.	池北雅彦, 堀江まどか, 服部正和, Akinori Morita and 船津修 : 腎症を発症した糖尿病に特異的に発現するアポEタンパク質, 日本薬学会第128年会, Mar. 2008.
111.	大篭友博, 船津修, 中家修一, Akinori Morita and 池北雅彦 : 細胞接着分子テレンセファリンに結合したN-型糖鎖の構造解析, 日本薬学会第128年会, Mar. 2008.
112.	猪又健太郎, 北島優美, 青山佳代子, 宮本知実, 中田健也, 長原礼宗, 船津修, Akinori Morita, 峯木茂, 椎名勇 and 池北雅彦 : タモキシフェン誘導体による血管新生メカニズムの解析, 日本薬学会第128年会, Mar. 2008.
113.	北島優美, 猪又健太郎, 青山佳代子, 宮本知実, 中田健也, 長原礼宗, 船津修, Akinori Morita, 椎名勇 and 池北雅彦 : 新規タモキシフェン類縁体の合成及び血管新生制御作用の解析, 日本薬学会第128年会, Mar. 2008.
114.	袴田真矢, 池北雅彦 and Akinori Morita : マクロファージの貪食活性化測定法の確立, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
115.	鈴木康太郎, 船津修, Akinori Morita, 斎藤慎一 and 池北雅彦 : SK-N-SH細胞から調製した神経様細胞SK-N-SH-Nを用いた神経分化機構の解析, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
116.	船津修, 長坂美歩, Akinori Morita and 池北雅彦 : 昆虫細胞と哺乳動物細胞で交差反応性を有する糖鎖エピトープの性状解析, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
117.	船津修, 長坂美歩, Akinori Morita and 池北雅彦 : ブタ膵臓からのシアル酸結合分子の精製・同定, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
118.	望月万里, Akinori Morita, 羽染芳宗, 井田紀子, 村田寛, 船津修, 菅原二三男 and 池北雅彦 : カバノアナタケから同定された新規アポトーシス誘導物質DDTCTの作用機構, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
119.	池北雅彦, 堀江まどか, 服部正和, Akinori Morita and 船津修 : 糖尿病性腎症に特異的タンパク質の探索と同定, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
120.	三ツ廣香里, 船津修, Akinori Morita and 池北雅彦 : ラット肝癌細胞株dRLh-84から得られたモノクローナル抗体2B12の性状解析, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
121.	大篭友博, 船津修, Akinori Morita and 池北雅彦 : 終脳特異的に発現する細胞接着分子テレンセファリンのN型糖鎖の構造解析, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
122.	池田聖樹, 雪澤俊輔, 倉持幸司, 小林進, 船津修, Akinori Morita and 池北雅彦 : エポラクタエン1bのアポトーシス誘導機序の解明, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
123.	Akinori Morita, 山元真一, 伊藤あずさ, 榎本敦, 松本義久, 船津修, 細井義夫, 鈴木紀夫 and 池北雅彦 : オルトバナジン酸ナトリウムによるp53転写非依存性アポトーシス抑制機構, 第30回日本分子生物学会年会・第80回日本生化学会大会合同大会, Dec. 2007.
124.	伊藤あずさ, Akinori Morita, 山元真一, 船津修 and 池北雅彦 : 放射線高感受性MOLT-4細胞株におけるp53依存性放射線誘発アポトーシス経路の解析, 日本放射線影響学会第50回大会, Nov. 2007.
125.	山元真一, Akinori Morita, 伊藤あずさ, 榎本敦, 松本義久, 船津修, 細井義夫, 鈴木紀夫 and 池北雅彦 : オルトバナジン酸ナトリウムによるp53制御メカニズムの解明, 日本放射線影響学会第50回大会, Nov. 2007.
126.	榎本敦, 木戸直樹, 伊藤道彦, Akinori Morita, 細井義夫 and 宮川清 : 新規MAP3K結合因子の機能解析, 日本放射線影響学会第50回大会, Nov. 2007.
127.	榎本敦, 木戸直樹, Akinori Morita, 細井義夫 and 宮川清 : 新規MAPKKK制御因子の機能解析とそれを標的とした増感, 第16回日本アポトーシス研究会学術集会, Aug. 2007.
128.	松本義久, BHOSLE Sushma M, 冨田雅典, 榎本敦, Akinori Morita, 鈴木紀夫, 細井義夫 and 宮川清 : NHEJ修復酵素群のDNA二重鎖切断部位への動員とリン酸化による制御, 日本放射線影響学会第49回大会, Sep. 2006.
129.	榎本敦, 木戸直樹, Akinori Morita, 伊藤道彦, 松本義久, 細井義夫 and 宮川清 : 新規JNKカスケード制御因子の機能解析とそれを標的としたアポトーシス増感, 日本放射線影響学会第49回大会, Sep. 2006.
130.	榎本敦, 木戸直樹, Akinori Morita, 伊藤道彦, 細井義夫 and 宮川清 : 新規MAPKKK抑制因子によるJNKカスケードの制御, 第15回日本アポトーシス研究会学術集会, Jul. 2006.
131.	細井義夫, 丹野悠司, 松本義久, 榎本敦, Akinori Morita, 高倉かほる and 宮川清 : 転写因子Sp1によるDNA2重鎖切断修復酵素の転写制御と放射線増感, 第65回日本医学放射線学会学術集会, Apr. 2006.
132.	ATSUSHI ENOMOTO, NAOKI KIDO, Akinori Morita, TAKAHIKO SUZUKI, YOSHIHISA MATSUMOTO, YOSHIO HOSOI and KIYOSHI MIYAGAWA : Regulation of MAPKKK of JNK cascade by a novel protein kinase, Tissue Culture Research Communications, Vol.25, No.1, 61, Mar. 2006. (Link to Search Site for Scientific Articles) ● CiNii @ National Institute of Informatics (CRID): 1570009750278973056 (CiNii: 1570009750278973056)
133.	榎本敦, Akinori Morita, 伊藤道彦, 宮川清 and 細井義夫 : 新規JIP結合キナーゼによるJNKカスケードの制御, 第28回日本分子生物学会年会, Dec. 2005.
134.	李智平, 細井義夫, 蔡克松, 丹野悠司, 松本義久, 榎本敦, Akinori Morita and 宮川清 : 放射線によるEGFRとERKの活性化に関わる情報伝達経路の検討, 日本放射線影響学会第48回大会, Nov. 2005.
135.	榎本敦, Akinori Morita, 伊藤道彦, 松本義久, 鈴木紀夫 and 細井義夫 : 新規JNKシグナル制御因子の機能解析, 日本放射線影響学会第48回大会, Nov. 2005.
136.	松本義久, 冨田雅典, 尹洪蘭, 酒井一夫, Akinori Morita, 榎本敦, 鈴木崇彦, 細井義夫 and 鈴木紀夫 : DNA-PKのタンパク質リン酸化機能はなぜDNA二重鎖切断修復において重要か?-「真の基質」XRCC4とリン酸化の意義, 日本放射線影響学会第48回大会, Nov. 2005.
137.	丹野悠司, 細井義夫, 李智平, 蔡克松, 松本義久, 榎本敦, Akinori Morita, 高倉かほる, 酒井一夫, 冨田雅典 and 宮川清 : Sp1によるDNA二重鎖切断修復関連遺伝子の転写制御, 日本放射線影響学会第48回大会, Nov. 2005.
138.	Akinori Morita, 榎本敦, 松本義久, 鈴木紀夫 and 細井義夫 : オルトバナジン酸ナトリウムによるDNA損傷誘導p53依存性アポトーシス抑制機構, 日本放射線影響学会第48回大会, Nov. 2005.
139.	松本義久, 冨田雅典, Akinori Morita, 細井義夫 and 鈴木紀夫 : DNA‐PKのタンパク質リン酸化機能はなぜDNA二重鎖切断修復において重要か?—「真の基質」XRCC4とリン酸化の意義, 第64回日本癌学会学術総会, Sep. 2005.
140.	榎本敦, Akinori Morita, 松本義久, 鈴木紀夫 and 細井義夫 : 新規JIP結合因子によるJNK cascdeの制御, 第14回日本アポトーシス研究会学術集会, Jul. 2005.
141.	Akinori Morita, 榎本敦, 松本義久 and 細井義夫 : オルトバナジン酸ナトリウムによるDNA損傷誘導p53依存性アポトーシス抑制機構, 第14回日本アポトーシス研究会学術集会, Jul. 2005.
142.	榎本敦, Akinori Morita, 伊藤道彦 and 細井義夫 : JNKスカフォールドタンパクJIP1と相互作用する因子の機能解析, 第27回日本分子生物学会年会, Dec. 2004.
143.	Akinori Morita, 鈴木紀夫, 榎本敦, 松本義久 and 細井義夫 : オルトバナジン酸ナトリウムによるDNA損傷誘発アポトーシス抑制機構, 第27回日本分子生物学会年会, Dec. 2004.
144.	尹洪蘭, 鈴木夕佳, 松本義久, 冨田雅典, Yoshiya Furusawa, 榎本敦, Akinori Morita, 青木瑞穂 and 鈴木紀夫 : 温熱による放射線増感の分子メカニズム:DNA二重鎖切断修復機構の関与について, 日本放射線影響学会第47回大会, Nov. 2004.
145.	榎本敦, Akinori Morita, 伊藤道彦, 松本義久 and 細井義夫 : ストレス応答キナーゼJNK経路における新規JIP結合タンパクの同定と機能解析, 日本放射線影響学会第47回大会, Nov. 2004.
146.	李智平, 細井義夫, 松本義久, 榎本敦 and Akinori Morita : 放射線によるEGF受容体活性化の機序に関する検討, 日本放射線影響学会第47回大会, Nov. 2004.
147.	細井義夫, 松本義久, 榎本敦 and Akinori Morita : 放射線増感・感受性予測の分子標的としてのDNA依存性プロテインキナーゼ, 日本放射線影響学会第47回大会, Nov. 2004.
148.	松本義久, 冨田雅典, 尹洪蘭, Akinori Morita, 榎本敦, 鈴木崇彦, 細井義夫, 大友邦 and 鈴木紀夫 : 放射線によるDNA損傷と修復の分子機構 DNA‐PKのタンパク質リン酸化機能はなぜDNA二重鎖切断修復において重要か?‐「真の基質」XRCC4とリン酸化の意義, 日本放射線影響学会第47回大会, Nov. 2004.
149.	Akinori Morita, 鈴木紀夫, 榎本敦, 松本義久 and 細井義夫 : オルトバナジン酸ナトリウムによるDNA損傷誘発アポトーシス抑制機構, 日本放射線影響学会第47回大会, Nov. 2004.
150.	松本義久, 冨田雅典, Akinori Morita, 細井義夫 and 鈴木紀夫 : DNA‐PKによるXRCC4リン酸化とDNA二重鎖切断修復・ゲノム安定性維持における意義, 第63回日本癌学会学術総会, Sep. 2004.
151.	Akinori Morita, 榎本敦, 松本義久, 鈴木紀夫 and 細井義夫 : オルトバナジン酸ナトリウムによる放射線誘発アポトーシス抑制機構, 第13回日本アポトーシス研究会学術集会, Jul. 2004.
152.	尹洪蘭, 鈴木夕佳, 松本義久, 冨田雅典, Yoshiya Furusawa, 榎本敦, Akinori Morita, 青木瑞穂 and 細井義夫 : ニワトリBリンパ球DT40細胞と相同組み換え,非相同組み換え欠損細胞の温熱放射線増感作用, 日本放射線影響学会第46回大会, Oct. 2003.
153.	松本義久, 梅田典子, 尹洪蘭, 冨田雅典, 榎本敦, Akinori Morita, 水越てるみ, 酒井一夫 and 鈴木紀夫 : 温熱のDNA依存性プロテインキナーゼ(DNA‐PK)に対する作用と放射線増感, 日本放射線影響学会第46回大会, Oct. 2003.
154.	榎本敦, Akinori Morita, 伊藤道彦, 細井義夫, 善岡克次 and 鈴木紀夫 : アポトーシスにおけるカスパーゼによるJNKの切断, 日本放射線影響学会第46回大会, Oct. 2003.
155.	Akinori Morita, 朱瑾, 鈴木紀夫, 榎本敦, 松本義久 and 細井義夫 : オルトバナジン酸ナトリウムによるアポトーシス抑制機構, 日本放射線影響学会第46回大会, Oct. 2003.
156.	浅野拓行, 細井義夫, 松本義久, 榎本敦, Akinori Morita, 小島周二 and 鈴木紀夫 : Suraminならびに外来性DNAによるEGF受容体リン酸化量の減少, 第62回日本癌学会学術総会, Sep. 2003.
157.	松本義久, 冨田雅典, Akinori Morita, 細井義夫 and 鈴木紀夫 : DNA依存性プロテインキナーゼ(DNA‐PK)Kuサブユニットの温熱不安定性と放射線増感, 第62回日本癌学会学術総会, Sep. 2003.
158.	Akinori Morita, 朱瑾, 鈴木紀夫, 榎本敦, 松本義久 and 細井義夫 : オルトバナジン酸ナトリウムによるアポトーシス抑制機構, 第62回日本癌学会学術総会, Sep. 2003.
159.	Akinori Morita, 朱瑾, 鈴木紀夫, 榎本敦, 松本義久 and 細井義夫 : オルトバナジン酸ナトリウムによるアポトーシス抑制機構, 第12回日本アポトーシス研究会学術集会, Aug. 2003.
160.	浅野拓行, 細井義夫, 松本義久, 榎本敦, Akinori Morita, 小島周二 and 鈴木紀夫 : SuraminによるEpidermal Growth Factor Receptor(EGFR)の活性化, 第61回日本癌学会学術総会, Oct. 2002.
161.	細井義夫, 松本義久, 榎本敦, Akinori Morita and 鈴木紀夫 : Phosphorothioate oligonucleotidesによるDNA依存性プロテインキナーゼ活性の阻害, 第61回日本癌学会学術総会, Oct. 2002.
162.	榎本敦, Akinori Morita, 伊藤道彦, 松本義久, 細井義夫, 善岡克次 and 鈴木紀夫 : アポトーシスの過程で新たに誘導されるJNKタンパクの解析, 日本放射線影響学会第45回大会, Sep. 2002.
163.	榎本敦, 康芸, 平野和也, Akinori Morita, 松本義久, 細井義夫, 酒井一夫 and 鈴木紀夫 : MOLT-4細胞のX線誘発細胞死におけるc-Mycの関与, 日本放射線影響学会第44回大会, Oct. 2001.
164.	松本義久, 南波直樹, 梅田典子, 冨田雅典, Akinori Morita, 芹沢しのぶ, 榎本敦, 細井義夫 and 鈴木紀夫 : X線照射後に見られるXRCC4タンパク質の切断とリン酸化, 第23回日本分子生物学会年会, Nov. 2000.
165.	Akinori Morita, 鈴木紀夫, 榎本敦 and 松本義久 : MOLT-4の放射線細胞死におけるp41生成機構, 日本放射線影響学会第43回大会, Aug. 2000.
166.	Akinori Morita, 鈴木紀夫, 榎本敦, 松本義久, 平野和也 and 酒井一夫 : アポトーシスの過程におけるp42タンパク質の修飾機構, 第57回日本癌学会学術総会, Oct. 1998.
167.	Akinori Morita, 鈴木紀夫, 榎本敦, 松本義久, 平野和也 and 酒井一夫 : MOLT-4の放射線細胞死におけるp41生成機構, 日本医学放射線学会第37回生物部会学術大会, Apr. 1998.

Et cetera, Workshop:

1.	Yuichi Nishiyama and Akinori Morita : 放射線のはたらきを最適化するp53制御性放射線防護剤の開発, 日本原子力学会中国・四国支部講演会, Jun. 2022.
2.	Akinori Morita : p53制御による放射線防護, 核化学夏の学校2016, Aug. 2016.

Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)

DNA損傷応答分子の制御によってがん制御率を高める放射線併用治療薬の開発 (Project/Area Number: 23K27550 )
Development of Combination Radiation Therapy Drugs to Improve Cancer Control Rates by Regulating DNA Damage Response Molecules (Project/Area Number: 23H02859 )
A novel radioprotective mechanism of sodium orthovanadate and its application to radiotherapy (Project/Area Number: 21K07644 )
Development of radioprotectors that selectively protect normal tissues (Project/Area Number: 19H03604 )
Development of novel radioprotectors that target p53 (Project/Area Number: 16K10396 )
Development of novel kind of radioprotectors that relieve the damage of normal tissues in radiation injury (Project/Area Number: 24689050 )
Development of novel kind of p53 inhibitorsthat target the zincbinding site of p53 (Project/Area Number: 21791218 )
効果的なp53阻害剤の開発 (Project/Area Number: 18790876 )
オルトバナジン酸ナトリウムによる放射線誘発アポトーシス抑制機講の解明 (Project/Area Number: 16790723 )
細胞応答シグナルを利用する新放射線療法の開発 (Project/Area Number: 16659325 )
放射線誘発アポトーシスにおけるp41機能の研究 (Project/Area Number: 14770447 )
応答特異抗体とDNA arrayによる放射線感受性予測システムの構築 (Project/Area Number: 14657211 )
Clarification of response mechanism in U937 cells against heat treatment (Project/Area Number: 14370271 )
放射線細胞応答メカニズムと感受性予測 (Project/Area Number: 12217029 )
Search by Researcher Number (90334234)

Professor : Morita, Akinori

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Grants-in-Aid for Scientific Research (KAKEN Grants Database @ NII.ac.jp)