MuRF1 deficiency prevents age-related fat weight gain, possibly through accumulation of PDK4 in skeletal muscle mitochondria in older mice


Crystal structure of inhibitor-bound human MSPL that can activate high pathogenic avian influenza.

Infection of certain influenza viruses is triggered when its HA is cleaved by host cell proteases such as proprotein convertases and type II transmembrane serine proteases (TTSP). HA with a monobasic motif is cleaved by trypsin-like proteases, including TMPRSS2 and HAT, whereas the multibasic motif found in high pathogenicity avian influenza HA is cleaved by furin, PC5/6, or MSPL. MSPL belongs to the TMPRSS family and preferentially cleaves [R/K]-K-K-R sequences. Here, we solved the crystal structure of the extracellular region of human MSPL in complex with an irreversible substrate-analog inhibitor. The structure revealed three domains clustered around the C-terminal α-helix of the SPD. The inhibitor structure and its putative model show that the P1-Arg inserts into the S1 pocket, whereas the P2-Lys and P4-Arg interacts with the Asp/Glu-rich 99-loop that is unique to MSPL. Based on the structure of MSPL, we also constructed a homology model of TMPRSS2, which is essential for the activation of the SARS-CoV-2 spike protein and infection. The model may provide the structural insight for the drug development for COVID-19.


Cytotoxicity of Benzophenone-3, an organic UV filter, is caused by increases of intracellular Zn2+ levels in rat thymocytes.

Benzophenone-3 (BP-3) is often used as an ultraviolet (UV) light filter in sunscreen products. Although BP-3 protects the human skin and hair from damage caused by excessive UV radiation, it is reported to exhibit toxic effects in human. However, the cytotoxicity of BP-3 on various cells is still not well understood. In the present study, the cytotoxicity of BP-3 against rat thymocytes was evaluated using a flow cytometric technique with fluorescent probes. Cell mortality increased significantly after 3 h of exposure to 300 M BP-3, whereas the mean intensity of 5-chloromethylfluorescein diacetate (5-CMF) fluorescence and cellular content of non-protein thiols decreased significantly. However, the membrane potential of thymocytes was not change by BP-3 treatment. Moreover, intracellular Zn levels increased significantly in a concentration-dependent manner in response to 30 M BP-3 or higher. The BP-3-induced changes in intracellular Zn levels and non-protein thiol content increased the vulnerability of thymocytes to oxidative stress. We concluded that BP-3-induced cytotoxicity may be caused by oxidative stress associated with an increase in intracellular Zn levels.


Neoadjuvant Chemotherapy with Gemcitabine Plus Nab-paclitaxel Reduces the Number of Cancer-associated Fibroblasts Through Depletion of Pancreatic Stroma.

In this study, the effects of neoadjuvant chemotherapy (NAC) on cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma were investigated. Density of -smooth muscle actin (SMA)-positive fibroblasts in resected surgical specimens from untreated patients, patients receiving conventional gemcitabine plus S-1 (GS), and patients receiving gemcitabine plus nab-paclitaxel (GnP) was determined by hybrid cell counting. 18F-Fluorodeoxyglucose positron-emission tomography (FDG-PET) scans and carbohydrate antigen 19-9 (CA19-9) concentrations were used to assess tumor activity before and after chemotherapy in the GnP group. In this retrospective study of 65 patients, SMA expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of SMA-positive fibroblasts. There were significantly fewer SMA-positive fibroblasts in the GnP than in the untreated and GS groups, but there was no significant difference between the latter two groups. SMA density reflected a decrease in standardized uptake value on FDG-PET, but not CA19-9 concentration, after GnP chemotherapy. These data suggest that the GnP regimen induces stromal depletion, resulting in fewer CAFs.


Type II cGMP-dependent protein kinase negatively regulates fibroblast growth factor signaling by phosphorylating Raf-1 at serine 43 in rat chondrosarcoma cells.

Although type II cGMP-dependent protein kinase (PKGII) is a major downstream effector of cGMP in chondrocytes and attenuates the FGF receptor 3/ERK signaling pathway, its direct target proteins have not been fully explored. In the present study, we attempted to identify PKGII-targeted proteins, which are associated with the inhibition of FGF-induced MAPK activation. Although FGF2 stimulation induced the phosphorylation of ERK1/2, MEK1/2, and Raf-1 at Ser-338 in rat chondrosarcoma cells, pretreatment with a cell-permeable cGMP analog strongly inhibited their phosphorylation. On the other hand, Ser-43 of Raf-1 was phosphorylated by cGMP in a dose-dependent manner. Therefore, we examined the direct phosphorylation of Raf-1 by PKGII. Wild-type PKGII phosphorylated Raf-1 at Ser-43 in a cGMP-dependent manner, but a PKGII D412A/R415A mutant, which has a low affinity for cGMP, did not. Finally, we found that a phospho-mimic mutant, Raf-1 S43D, suppressed FGF2-induced MAPK pathway. These results suggest that PKGII counters FGF-induced MEK/ERK activation through the phosphorylation of Raf-1 at Ser-43 in chondrocytes.

Biochemical and Biophysical Research Communications


Protein purification and cloning of diacylglycerol lipase from rat brain.

Diacylglycerol (DG) lipase, which hydrolyses 1-stearoyl-2-arachidonyl-sn-glycerol to produce an endocannabinoid, 2-arachidonoylglycerol, was purified from the soluble fraction of rat brain lysates. DG lipase was purified about 1,200-fold by a sequential column chromatographic procedure. Among proteins identified by mass spectrometry analysis in the partially purified DG lipase sample, only DDHD domain containing two (DDHD2), which was formerly regarded as a phospholipase A1, exhibited significant DG lipase activity. Rat DDHD2 expressed in Chinese hamster ovary cells showed similar enzymatic properties to partially purified DG lipase from rat brain. The source of DG lipase activity in rat brain was immunoprecipitated using anti-DDHD2 antibody. Thus, we concluded that the DG lipase activity in the soluble fraction of rat brain is derived from DDHD2. DDHD2 is distributed widely in the rat brain. Immunohistochemical analysis revealed that DDHD2 is expressed in hippocampal neurons, but not in glia.


Neutralization of leukotriene C4 and D4 activity by monoclonal and single-chain antibodies.

Cysteinyl leukotrienes (LTs) are key mediators in inflammation. To explore the structure of the antigen-recognition site of a monoclonal antibody against LTC4 (mAbLTC), we previously isolated full-length cDNAs for heavy and light chains of the antibody and prepared a single-chain antibody comprising variable regions of these two chains (scFvLTC). We examined whether mAbLTC and scFvLTC neutralized the biological activities of LTC4 and LTD4 by competing their binding to their receptors. mAbLTC and scFvLTC inhibited their binding of LTC4 or LTD4 to CysLT1 receptor (CysLT1R) and CysLT2 receptor (CysLT2R) overexpressed in Chinese hamster ovary cells. The induction by LTD4 of monocyte chemoattractant protein-1 and interleukin-8 mRNAs in human monocytic leukemia THP-1 cells expressing CysLT1R was dose-dependently suppressed not only by mAbLTC but also by scFvLTC. LTC4- and LTD4-induced aggregation of mouse platelets expressing CysLT2R was dose-dependently suppressed by either mAbLTC or scFvLTC. Administration of mAbLTC reduced pulmonary eosinophil infiltration and goblet cell hyperplasia observed in a murine model of asthma. Furthermore, mAbLTC bound to CysLT2R antagonists but not to CysLT1R antagonists. These results indicate that mAbLTC and scFvLTC neutralize the biological activities of LTs by competing their binding to CysLT1R and CysLT2R. Furthermore, the binding of cysteinyl LT receptor antagonists to mAbLTC suggests the structural resemblance of the LT-recognition site of the antibody to that of these receptors. mAbLTC can be used in the treatment of inflammatory diseases such as asthma.

Biochimica et Biophysica Acta (BBA) - General Subjects


新規脳ジアシルグリセロールリパーゼの同定.

新規脳ジアシルグリセロールリパーゼの同定.

Proceedings of the Japanese Conference on the Biochemistry of Lipids


ロイコトリエン作用に対する抗ロイコトリエンC4単鎖抗体の中和効果.

ロイコトリエン作用に対する抗ロイコトリエンC4単鎖抗体の中和効果.


Gタンパク質共役型受容体，G2Aを介したがん幹細胞性制御.

Gタンパク質共役型受容体，G2Aを介したがん幹細胞性制御.


Azelnidipine is a calcium blocker that attenuates liver fibrosis and may increase antioxidant defense.

Oxidative stress plays a critical role in liver fibrogenesis. Reactive oxygen species (ROS) stimulate hepatic stellate cells (HSCs), and ROS-mediated increases in calcium influx further increase ROS production. Azelnidipine is a calcium blocker that has been shown to have antioxidant effects in endothelial cells and cardiomyocytes. Therefore, we evaluated the anti-fibrotic and antioxidative effects of azelnidipine on liver fibrosis. We used TGF-β1-activated LX-2 cells (a human HSC line) and mouse models of fibrosis induced by treatment with either carbon tetrachloride (CCl(4) ) or thioacetamide (TAA). Azelnidipine inhibited TGF-β1 and angiotensin II (Ang II)-activated α1(I) collagen mRNA expression in HSCs. Furthermore, TGF-β1- and Ang II-induced oxidative stress and TGF-β1-induced p38 and JNK phosphorylation were reduced in HSCs treated with azelnidipine. Azelnidipine significantly decreased inflammatory cell infiltration, pro-fibrotic gene expressions, HSC activation, lipid peroxidation, oxidative DNA damage and fibrosis in the livers of CCl(4) - or TAA-treated mice. Finally, azelnidipine prevented a decrease in the expression of some antioxidant enzymes and accelerated regression of liver fibrosis in CCl(4) -treated mice. Azelnidipine inhibited TGF-β1- and Ang II-induced HSC activation in vitro and attenuated CCl(4) - and TAA-induced liver fibrosis, and it accelerated regression of CCl(4) -induced liver fibrosis in mice. The anti-fibrotic mechanism of azelnidipine against CCl(4) -induced liver fibrosis in mice may have been due an increased level of antioxidant defence. As azelnidipine is widely used in clinical practice without serious adverse effects, it may provide an effective new strategy for anti-fibrotic therapy.


哺乳動物のGDE群とマウスGDE5の非酵素的機構による骨格筋分化制御.

哺乳動物のGDE群とマウスGDE5の非酵素的機構による骨格筋分化制御.


Neuronal pentraxin 1 induction in hypoxic-ischemic neuronal death is regulated via a glycogen synthase kinase-3α/β dependent mechanism.

Intracellular signaling pathways that regulate the production of lethal proteins in central neurons are not fully characterized. Previously, we reported induction of a novel neuronal protein neuronal pentraxin 1 (NP1) in neonatal brain injury following hypoxia-ischemia (HI); however, how NP1 is induced in hypoxic-ischemic neuronal death remains elusive. Here, we have elucidated the intracellular signaling regulation of NP1 induction in neuronal death. Primary cortical neurons showed a hypoxic-ischemia time-dependent increase in cell death and that NP1 induction preceded the actual neuronal death. NP1 gene silencing by NP1-specific siRNA significantly reduced neuronal death. The specificity of NP1 induction in neuronal death was further confirmed by using NP1 (-/-) null primary cortical neurons. Declines in phospho-Akt (i.e. deactivation) were observed concurrent with decreased phosphorylation of its downstream substrate GSK-3α/β (at Ser21/Ser9) (i.e. activation) and increased GSK-3α and GSK-3β kinase activities, which occurred prior to NP1 induction. Expression of a dominant-negative inhibitor of Akt (Akt-kd) blocked phosphorylation of GSK-3α/β and subsequently enhanced NP1 induction. Whereas, overexpression of constitutively activated Akt (Akt-myr) or wild-type Akt (wtAkt) increased GSK-α/β phosphorylation and attenuated NP1 induction. Transfection of neurons with GSK-3α siRNA completely blocked NP1 induction and cell death. Similarly, overexpression of the GSK-3β inhibitor Frat1 or the kinase mutant GSK-3βKM, but not the wild-type GSK-3βWT, blocked NP1 induction and rescued neurons from death. Our findings clearly implicate both GSK-3α- and GSK-3β-dependent mechanism of NP1 induction and point to a novel mechanism in the regulation of hypoxic-ischemic neuronal death.


Cytosolic phospholipase A2alpha amplifies early cyclooxygenase-2 expression, oxidative stress and MAP kinase phosphorylation after cerebral ischemia in mice.

The enzyme cytosolic phospholipase A2 alpha (cPLA2alpha) has been implicated in the progression of cerebral injury following ischemia and reperfusion. Previous studies in rodents suggest that cPLA2alpha enhances delayed injury extension and disruption of the blood brain barrier many hours after reperfusion. In this study we investigated the role of cPLA2alpha in early ischemic cerebral injury. Middle cerebral artery occlusion (MCAO) was performed on cPLA2alpha+/+ and cPLA2alpha-/- mice for 2 hours followed by 0, 2, or 6 hours of reperfusion. The levels of cPLA2alpha, cyclooxygenase-2, neuronal morphology and reactive oxygen species in the ischemic and contralateral hemispheres were evaluated by light and fluorescent microscopy. PGE2 content was compared between genotypes and hemispheres after MCAO and MCAO and 6 hours reperfusion. Regional cerebral blood flow was measured during MCAO and phosphorylation of relevant MAPKs in brain protein homogenates was measured by Western analysis after 6 hours of reperfusion. Neuronal cPLA2alpha protein increased by 2-fold immediately after MCAO and returned to pre-MCAO levels after 2 hours reperfusion. Neuronal cyclooxygenase-2 induction and PGE2 concentration were greater in cPLA2alpha+/+ compared to cPLA2alpha-/- ischemic cortex. Neuronal swelling in ischemic regions was significantly greater in the cPLA2alpha+/+ than in cPLA2alpha-/- brains (+/+:2.2+/-0.3 fold vs. -/-:1.7+/-0.4 fold increase; P<0.01). The increase in reactive oxygen species following 2 hours of ischemia was also significantly greater in the cPLA2alpha+/+ ischemic core than in cPLA2alpha-/- (+/+:7.12+/-1.2 fold vs. -/-:3.1+/-1.4 fold; P<0.01). After 6 hours of reperfusion ischemic cortex of cPLA2alpha+/+, but not cPLA2alpha-/-, had disruption of neuron morphology and decreased PGE2 content. Phosphorylation of the MAPKs-p38, ERK 1/2, and MEK 1/2-was significantly greater in cPLA2a+/+ than in cPLA2alpha-/- ischemic cortex 6 hours after reperfusion. These results indicate that cPLA2alpha modulates the earliest molecular and injury responses after cerebral ischemia and have implications for the potential clinical use of cPLA2alpha inhibitors.


Novel function of 9(S)-hydroxyoctadecadienoic acid on proliferation of T cells.


Cytosolic phospholipase A(2) alpha mediates electrophysiologic responses of hippocampal pyramidal neurons to neurotoxic NMDA treatment.

The arachidonic acid-generating enzyme cytosolic phospholipase A(2) alpha (cPLA(2)alpha) has been implicated in the progression of excitotoxic neuronal injury. However, the mechanisms of cPLA(2)alpha toxicity have yet to be determined. Here, we used a model system exposing mouse hippocampal slices to NMDA as an excitotoxic injury, in combination with simultaneous patch-clamp recording and confocal Ca(2+) imaging of CA1 pyramidal neurons. NMDA treatment caused significantly greater injury in wild-type (WT) than in cPLA(2)alpha null CA1 neurons. Bath application of NMDA evoked a slow inward current in voltage-clamped neurons (composed of both NMDA receptor-mediated and other conductances) that was smaller in cPLA(2)alpha null than in WT slices. This was not due to down-regulation of NMDA receptor function because NMDA receptor-mediated currents were equivalent in each genotype following brief photolysis of caged glutamate. Current-clamp recordings were made during and following NMDA exposure by eliciting a single action potential with a brief current injection. After NMDA exposure, WT CA1 neurons developed a spike-evoked plateau potential and an increased spike-evoked dendritic Ca(2+) transient. These effects were absent in CA1 neurons from cPLA(2)alpha null mice and WT neurons treated with a cPLA(2)alpha inhibitor. The Ca-sensitive K-channel toxins, apamin and paxilline, caused spike broadening and Ca(2+) enhancement in WT and cPLA(2)alpha null slices. NMDA application in WT and arachidonate applied to cPLA(2)alpha null cells occluded the effects of apamin/paxilline. These results indicate that cPLA(2)alpha activity is required for development of aberrant electrophysiologic events triggered by NMDA receptor activation, in part through attenuation of K-channel function.

Proceedings of the National Academy of Sciences of the United States of America


Cytosolic phospholipase A2 alpha modulates NMDA neurotoxicity in mouse hippocampal cultures.

The arachidonic acid-specific cytosolic phospholipase A(2) alpha (cPLA(2)alpha) has been implicated in the generation of neurological injuries. cPLA(2)alpha-dependent neurological injury has been postulated to be mediated through inflammatory and eicosanoid pathways. We determined if cPLA(2)alpha amplifies the injury of a non-inflammatory, excitotoxic stimulus by modifying a well-described toxicity assay to measure the toxicity of N-methyl-d-aspartate (NMDA) in the CA1 region of organotypic, mouse hippocampal cultures. Hippocampal cultures from wild-type and cPLA(2)alpha knockout mice were exposed to 5, 7.5 or 10 microm NMDA for 1 h. Toxicity was measured 23 h later. Cultures derived from cPLA(2)alpha(-/-) mice and cultures treated with the selective inhibitor AACOCF(3) were significantly protected from NMDA toxicity, as compared with wild-type cultures. To determine if cPLA(2)alpha-dependent toxicity is cyclooxygenase (COX)-2 dependent, COX-2 and PGE(2) levels were measured 7 and 25 h after NMDA treatment. NMDA treatment failed to induce COX-2 protein or increase PGE(2) in the culture media in either genotype at either time. In contrast, phorbol 12-myristate 13-acetate and ionophore treatment caused robust induction of COX-2 and PGE(2) in both genotypes. We conclude that cPLA(2)alpha may have a hitherto unrecognized direct effect on excitatory neurotoxicity, suggesting that cPLA(2)alpha inhibition is a therapeutic candidate for treatment of the early, excitotoxic injury observed in stroke.


Profiling of eicosanoid production in the rat hippocampus during kainic acid-induced seizure: dual phase regulation and differential involvement of COX-1 and COX-2.

Kainic acid (KA)-induced seizure in rat involves eicosanoid production in the brain, but their production mechanism and biological functions are poorly understood. We profiled the eicosanoid production during KA-induced seizure by a comprehensive lipidomics analysis using liquid chromatography-tandem mass spectrometry. Systemic KA administration caused production of large amounts of prostaglandin (PG) F(2alpha) and PGD(2) in the hippocampus, with smaller amounts of other PGs and hydroxyeicosatetraenoic acids. The production was biphasic, which consisted of an initial burst in the first 30 min and a sustained late phase production. The initial phase was specific to the hippocampus and was blocked by intracerebroventricular administration of KA receptor antagonists. A selective cyclooxygenase (COX)-2 inhibitor, NS398, completely inhibited the initial phase productions, except for PGD(2) and thromboxane B(2), whose productions were also dependent on COX-1. These results suggest that KA signals directly stimulate the arachidonic acid cascade in the initial phase and that COX-1 and COX-2, both constitutively expressed at low levels, differentially contribute to PG productions. In the late phase, a sustained PG production in hippocampus appears due to the increased COX-2 levels even with a limited arachidonic acid supply. The present study demonstrates a dual phase regulatory mechanism of eicosanoid production during KA-induced seizure, providing a biochemical basis for understanding the biosynthesis and roles of eicosanoids in the brain.


てんかん様痙攣刺激による脂質メディエーター及びその産生分子群の発現プロファイリング.


Localization of cytosolic phospholipase A2 messenger RNA mainly in neurons in the rat brain.


Major population of 85-kDa cytosolic phospholipase A2 mRNA signals localized in neurons in rat brain.


Arachidonate 12-lipoxygenases. Catalytic properties and regulation of the enzyme gene.

Advances in Experimental Medicine and Biology


New probes for in vivo measurements of cell proliferation, antisense oligonucleotides pharmacokinetics, and receptor occupancy in acetylcholinergic and NK systems by using positron emission tomography.


アラキドン酸酸素添加酵素の自殺的失活.

アラキドン酸酸素添加酵素の自殺的失活.

Proceedings of the Japanese Conference on the Biochemistry of Lipids


Lipoxygenase-Catalyzed Transformation of Its Primry Hydroperoxy Product.


ブタ白血球12-リポキシゲナーゼの自殺的失活に伴う酵素蛋白への15-ヒドロペルオキシエイコサテトラエン酸の取り込み.


Suicide inactivation of porcine leukocyte 12-lipoxygenase associated with its incorporation of 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid derivative.

Two isozymes of arachidonate 12-lipoxygenase, platelet-type and leukocyte-type, which were distinguished by their substrate specificities and primary structures, were investigated with reference to 'suicide' inactivation. Upon reaction with arachidonic acid the leukocyte-type enzyme was inactivated rapidly during the catalysis, whereas the platelet-type enzyme did not show such a rapid inactivation. The two 12-lipoxygenase isozymes were incubated with various hydroperoxy and hydroxy products from arachidonic acid. (15S)-Hydroperoxy-5,8,11,13-eicosatetraenoic acid (15-HPETE) was found to be a unique substrate of the leukocyte-type 12-lipoxygenase as follows. (1) 15-HPETE was an active substrate for porcine leukocyte 12-lipoxygenase, and converted anaerobically to a 14,15-epoxy compound (14,15-leukotriene A4). (2) A rapid inactivation of the enzyme was observed within 2 min upon aerobic and anaerobic incubations with 15-HPETE. (3) 15-HPETE was rapidly incorporated into the enzyme in a nearly equimolar amount under both aerobic and anaerobic conditions. (4) Several findings suggested a covalent binding of 15-HPETE or its derivative to the enzyme. (5) Such a rapid and stoichiometric incorporation of 15-HPETE was not observed with the platelet-type 12-lipoxygenase. On the basis of these findings we presumed that 15-HPETE was transformed to 14,15-leukotriene A4, which was covalently bound to the leukocyte-type 12-lipoxygenase leading to the suicide inactivation of the enzyme.

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism


15-ヒドロペルオキシエイコサテトラエン酸のブタ白血球12-リポキシゲナーゼへの取り込みと酵素の自殺的失活.


Immunocytochemical localization of platelet-type arachidonate 12-lipoxygenase in mouse blood cells.

The Journal of Histochemistry and Cytochemistry


Site-directed mutagenesis studies on the iron-binding domain and the determinant for the substrate oxygenation site of porcine leukocyte arachidonate 12-lipoxygenase.

cDNA for arachidonate 12-lipoxygenase of porcine leukocytes was expressed in Escherichia coli. The recombinant 12-lipoxygenase was purified by immunoaffinity chromatography to near homogeneity with a specific activity of about 1.5 mumol/min per mg protein. Each of eight histidine residues, which were well-conserved among various mammalian lipoxygenases and presumed as ligands for non-heme iron, was substituted with leucine by site-directed mutagenesis. Each mutant enzyme was immunoaffinity-purified to near homogeneity. Mutations of His-361, -366 and -541 caused a total loss of enzyme activity, and the iron content was much lower (0.10, 0.06 and 0.06 g atom/mol protein) than that of the wild-type enzyme (0.53). Mutations of His-128 and -356 gave 159% and 162% specific activity of the wild-type enzyme, and the iron contents were 0.55 and 0.52 g atom/mol protein. Substitution of His-426 decreased the activity to 5%, but the iron content was 0.4 g atom/mol protein. The expression level of mutants at His-384 and -393 was too low to precisely determine the iron content. Taken together, His-361, -366 and -541 may play important roles for iron-binding in catalytically active 12-lipoxygenase. Since a high homology of amino acid sequence was known between porcine leukocyte 12-lipoxygenase and mammalian 15-lipoxygenases, we attempted to convert the 12-lipoxygenase to a 15-lipoxygenase. A double mutation of Val-418 and -419 to Ile and Met increased the ratio of 15- and 12-lipoxygenase activities from 0.1 to 5.7.


アラキドン酸12-リポキシゲナーゼ反応におけるヒスチジン残基の役割.

アラキドン酸12-リポキシゲナーゼ反応におけるヒスチジン残基の役割.


ブタ白血球のアラキドン酸12-リポキシゲナーゼの部位特異的変異法による解析.

ブタ白血球のアラキドン酸12-リポキシゲナーゼの部位特異的変異法による解析.


Biochemical and molecular biological approaches to two types of arachidonate 12-lipoxygenase


Molecular structure and function of the porcine arachidonate 12-lipoxygenase gene.


血小板および白血球の12-リポキシゲナーゼのcDNAクローニングと遺伝子発現.

血小板および白血球の12-リポキシゲナーゼのcDNAクローニングと遺伝子発現.


Cellular oxygen-sensing and potassium channels.