The Japanese Journal of Clinical Nutrition


廃用性筋萎縮の機序とその予防

廃用性筋萎縮の機序とその予防

実験医学増刊号「健康寿命の鍵を握る骨格筋」

実験医学増刊号「健康寿命の鍵を握る骨格筋」


Japan's manned space program and space bioscience research

日本の有人宇宙開発と宇宙生物科学研究

Journal of Clinical and Experimental Medicine


Development of functional foods effective for bedridden and weightlessness-induced muscle atrophy

寝たきりや無重力による筋萎縮に有効な機能性食材の開発

Journal for the Integrated Study of Dietary Habits


Polyphenols and Their Effects on Muscle Atrophy and Muscle Health

Skeletal muscle atrophy is the decrease in muscle mass and strength caused by reduced protein synthesis/accelerated protein degradation. Various conditions, such as denervation, disuse, aging, chronic diseases, heart disease, obstructive lung disease, diabetes, renal failure, AIDS, sepsis, cancer, and steroidal medications, can cause muscle atrophy. Mechanistically, inflammation, oxidative stress, and mitochondrial dysfunction are among the major contributors to muscle atrophy, by modulating signaling pathways that regulate muscle homeostasis. To prevent muscle catabolism and enhance muscle anabolism, several natural and synthetic compounds have been investigated. Recently, polyphenols (i.e., natural phytochemicals) have received extensive attention regarding their effect on muscle atrophy because of their potent antioxidant and anti-inflammatory properties. Numerous in vitro and in vivo studies have reported polyphenols as strongly effective bioactive molecules that attenuate muscle atrophy and enhance muscle health. This review describes polyphenols as promising bioactive molecules that impede muscle atrophy induced by various proatrophic factors. The effects of each class/subclass of polyphenolic compounds regarding protection against the muscle disorders induced by various pathological/physiological factors are summarized in tabular form and discussed. Although considerable variations in antiatrophic potencies and mechanisms were observed among structurally diverse polyphenolic compounds, they are vital factors to be considered in muscle atrophy prevention strategies.


Findings from recent studies by the Japan Aerospace Exploration Agency examining musculoskeletal atrophy in space and on Earth

The musculoskeletal system provides the body with correct posture, support, stability, and mobility. It is composed of the bones, muscles, cartilage, tendons, ligaments, joints, and other connective tissues. Without effective countermeasures, prolonged spaceflight under microgravity results in marked muscle and bone atrophy. The molecular and physiological mechanisms of this atrophy under unloaded conditions are gradually being revealed through spaceflight experiments conducted by the Japan Aerospace Exploration Agency using a variety of model organisms, including both aquatic and terrestrial animals, and terrestrial experiments conducted under the Living in Space project of the Japan Ministry of Education, Culture, Sports, Science, and Technology. Increasing our knowledge in this field will lead not only to an understanding of how to prevent muscle and bone atrophy in humans undergoing long-term space voyages but also to an understanding of countermeasures against age-related locomotive syndrome in the elderly.


微小重力環境を利用した筋萎縮機構の研究

微小重力環境を利用した筋萎縮機構の研究


機能性宇宙食の開発について

機能性宇宙食の開発について


Mitochondria-mediated mechanosensing mechanism in skeletal muscle

筋ミトコンドリアによる重力感知


微小重力環境における筋萎縮発生メカニズムへの新展開

微小重力環境における筋萎縮発生メカニズムへの新展開


サルコペニアとメカニカルストレス

サルコペニアとメカニカルストレス


The skeletal muscle circadian clock: current insights


Involvement of Cbl-b-mediated macrophage inactivation in insulin resistance.

Aging and overnutrition cause obesity in rodents and humans. It is well-known that obesity causes various diseases by producing insulin resistance (IR). Macrophages infiltrate the adipose tissue (AT) of obese individuals and cause chronic low-level inflammation associated with IR. Macrophage infiltration is regulated by the chemokines that are released from hypertrophied adipocytes and the immune cells in AT. Saturated fatty acids are recognized by toll-like receptor 4 (TLR4) and induce inflammatory responses in AT macrophages (ATMs). The inflammatory cytokines that are released from activated ATMs promote IR in peripheral organs, such as the liver, skeletal muscle and AT. Therefore, ATM activation is a therapeutic target for IR in obesity. The ubiquitin ligase Casitas b-lineage lymphoma-b (Cbl-b) appears to potently suppress macrophage migration and activation. Cbl-b is highly expressed in leukocytes and negatively regulates signals associated with migration and activation. Cbl-b deficiency enhances ATM accumulation and IR in aging- and diet-induced obese mice. Cbl-b inhibits migration-related signals and SFA-induced TLR4 signaling in ATMs. Thus, targeting Cbl-b may be a potential therapeutic strategy to reduce the IR induced by ATM activation. In this review, we summarize the regulatory functions of Cbl-b in ATMs.


[Impacts of physical exercise on remodeling and hypertrophy of skeletal muscle.]

The skeletal muscle has high sensitivity for the mechanical stress. Because it is enlarged by training, whereas it is easily withered by lack of exercise. When we exercise, skeletal muscle cells per se sense mechanical loading, and muscular remodeling and the muscular hypertrophy occur. It has been revealed that the intracellular signaling through PGC-1 participates in the remodeling of the skeletal muscle, while PGC-14, an isoform of PGC-1, and the dystrophin-glycoprotein complex play important roles in muscular hypertrophy. This review describes the impact of physical exercise gives on the remodeling and hypertrophy of muscle through the signaling.


[Plasticity of skeletal muscle against unloading stress.]

Recently, muscle atrophy caused by unloading, such as spaceflight and bed rest has been becoming a social problem in Japan. However, the effective countermeasures against these disuse atrophy have not been developed. We have reviewed the mechanisms of disuse atrophy and its possible countermeasures.


Ubiquitin ligase Cbl-b and obesity-induced insulin resistance.

Obesity causes type 2 diabetes, atherosclerosis and cardiovascular diseases by inducing systemic insulin resistance. It is now recognized that obesity is related to chronic low-grade inflammation in adipose tissue. Specifically, activated immune cells infiltrate adipose tissue and cause inflammation. There is increasing evidence that activated macrophages accumulate in the hypertrophied adipose tissue of rodents and humans and induce systemic insulin resistance by secreting inflammatory cytokines. Accordingly, a better understanding of the molecular mechanisms underlying macrophage activation in adipose tissue will facilitate the development of new therapeutic strategies. Currently, little is known about the regulation of macrophage activation, although E3 ubiquitin ligase Casitas B-lineage lymphoma (Cbl)-b was identified recently as a novel negative regulator of macrophage activation in adipose tissue. Cbl-b, which is a suppressor of T- and B-cell activation, inhibits intracellular signal transduction by targeting some tyrosine kinases. Notably, preventing Cbl-b-mediated macrophage activation improves obesity-induced insulin resistance in mice. c-Cbl is another member of the Cbl family that is associated with insulin resistance in obesity. These reports suggest that Cbl-b and c-Cbl are potential therapeutic targets for treating obesity-induced insulin resistance. In this review, we focus on the importance of Cbl-b in macrophage activation in aging-induced and high-fat diet-induced obesity.


免疫とインスリン抵抗性ーユビキチンリガーゼCbl-bを中心にー

免疫とインスリン抵抗性ーユビキチンリガーゼCbl-bを中心にー

内分泌・糖尿病・代謝内科

内分泌・糖尿病・代謝内科


宇宙飛行と加齢による筋萎縮と栄養対策

宇宙飛行と加齢による筋萎縮と栄養対策


[Space flight/bedrest immobilization and bone. Space flight and bed rest-mediated muscle atrophy].

Muscle atrophy caused by unloading stress is a challenging problem for bed-rested patients or astronauts. However, countermeasures against these muscle atrophy have not been developed yet. Under unloading conditions, skeletal muscle mass is rapidly lost by the increase in protein breakdown and the decrease in protein synthesis. It has been shown that this enhancement of proteolysis in atrophying muscles results mainly from activation of the ubiquitin-proteasome proteolytic pathway. Previous our studies revealed that unloading stress led to skeletal muscle atrophy through the induction of ubiquitin ligase, Cbl-b (Casitas B-lineage lymphoma b) expression. Thus, Cbl-b inhibiters may be potent therapeutic and preventive sources against skeletal muscle atrophy caused by unloading stress.


[Space flight/bedrest immobilization and bone. Development of inhibitors for atrophy caused by unloading stress].

Muscle atrophy caused by unloading stress is a serious problem in bed rest patients or astronauts. In our previous studies, we revealed that induction and activation of ubiquitin ligase Cbl-b played an important role in skeletal muscle atrophy caused by unloading stress. Under muscle atrophy conditions, Cbl-b interacted with and degraded IRS-1 (insulin receptor substrate 1) that is a central molecule in the IGF-1 signaling pathway. In addition, we developed a Cbl-b inhibitor (Cblin) that a pentapeptide mimetic of tyrosin608-phosphorylated IRS-1, DGpYMP. This Cblin peptide inhibited Cbl-b mediated IRS-1 ubiquitination and strongly decreased the Cbl-b-mediated induction of MAFbx/atrogin-1. We are further developing Cbl-b inhibitors that are more effective than an original Cblin peptide.


Development of the studies on physiological functions of flavonoids

フラボノイドの生理機能性研究の展開


徳島大学栄養学発''宇宙実験''の歩みとこれから

徳島大学栄養学発''宇宙実験''の歩みとこれから


Ubiquitin Ligase Cbl-B Mediates the Atrophy of Bone and Skeletal Muscle during Unloading(Elucidation of Mechanisum of Muscular Atrophy and Rehabilitation,43rd Annual Meeting of the Japanese Association of Rehabilitation Medicine)

ユビキチンリガーゼCbl-b による運動器の廃用性萎縮

The Japanese Journal of Rehabilitation Medicine


骨芽細胞に対するアンローディングの影響

骨芽細胞に対するアンローディングの影響


生体におけるアミノ酸代謝

生体におけるアミノ酸代謝


無重力による筋萎縮と蛋白質分解酵素

無重力による筋萎縮と蛋白質分解酵素

週刊 医学のあゆみ 運動器科学の創生

週刊 医学のあゆみ 運動器科学の創生


栄養と免疫機能:ビタミンAと腸管免疫

栄養と免疫機能:ビタミンAと腸管免疫


アミノ酸生理作用:とくにシステイン

アミノ酸生理作用:とくにシステイン


筋萎縮を改善できる新しい宇宙食の開発をめざして

筋萎縮を改善できる新しい宇宙食の開発をめざして


サイトカイン受容体欠損マウスを用いた小腸粘膜免疫能に対するビタミンAの賦活効果の解析


代謝・免疫器官としての腸管:腸管局所免疫に対するビタミンAの効果

代謝・免疫器官としての腸管:腸管局所免疫に対するビタミンAの効果


ストレスと栄養:ストレスと蛋白質栄養

ストレスと栄養:ストレスと蛋白質栄養


Implications of heat shock/stress proteins for medicine and disease

Heat shock/stress proteins (HSPs) are crucial for maintenance of cellular homeostasis during normal cell growth and for survival during and after various cellular stresses. The HSP70 family functions as molecular chaperones and reduces stress-induced denaturation and aggregation of intracellular proteins. In addition to the chaperoning activities, HSP70 has been suggested to exert its protective action by protecting mitochondria and by interfering with the stress-induced apoptotic program. The biochemical and functional properties of HSPs observed in cultured cells may be relevant to organs and tissues in whole animals. The activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nerve system elicits the stress response in selected peripheral tissues; the HSP70 expression in the vasculature and stomach increases resistance against hemodynamic stress and stress-induced mucosal damage, respectively. Gastric mucosa pretreated with mild irritants acquires a tolerance against subsequent mucosal-damaging insults. This phenomenon is known as "adaptive cytoprotection". Transient ischemia also induces ischemic tolerance in the brain and heart, which is called "ischemic preconditioning". The heat shock response is believed to contribute to the acquisition of the tolerance. The therapeutic applications of chaperone inducers that induce HSPs without any toxic effect are also introduced.

The Journal of Medical Investigation : JMI


脂溶性ビタミンをめぐる新展開:新しいF9レポーター細胞に対するレチノイドとカロテノイドの分化誘導作用とその分子機構

Journal of Clinical and Experimental Medicine


消化器疾患ー分子生物学的アプローチ発生・生理への分子生物学的アプローチー小腸上皮細胞の分化と分子生物学:レチノイン酸とTGF-βによる分子誘導機序を中心として


消化管粘膜細胞と細胞増殖因子:小腸上皮細胞と増殖因子

消化管粘膜細胞と細胞増殖因子:小腸上皮細胞と増殖因子


骨吸収におけるカテプシンの役割

骨吸収におけるカテプシンの役割


システインプロテアーゼインヒビターによる骨粗鬆症の治療の可能性

システインプロテアーゼインヒビターによる骨粗鬆症の治療の可能性


令和3年度 徳島大学高等教育研究センターアドミッション部門 報告書

令和3年度 徳島大学高等教育研究センターアドミッション部門 報告書

令和3年度 徳島大学高等教育研究センターアドミッション部門 報告書

令和3年度 徳島大学高等教育研究センターアドミッション部門 報告書


平成30年度 徳島大学総合教育センターアドミッション部門 報告書

平成30年度 徳島大学総合教育センターアドミッション部門 報告書

平成30年度 徳島大学総合教育センターアドミッション部門 報告書

平成30年度 徳島大学総合教育センターアドミッション部門 報告書


平成29年度 徳島大学総合教育センターアドミッション部門 報告書

平成29年度 徳島大学総合教育センターアドミッション部門 報告書

平成29年度 徳島大学総合教育センターアドミッション部門 報告書

平成29年度 徳島大学総合教育センターアドミッション部門 報告書


ラット骨格筋遺伝子の宇宙フライトによる発現変動

ラット骨格筋遺伝子の宇宙フライトによる発現変動


宇宙フライトラットの骨格筋で発現の増大する新規遺伝子Sfigのフローニング

宇宙フライトラットの骨格筋で発現の増大する新規遺伝子Sfigのフローニング


徳島大学先端医療開発研究センター設置準備室成果報告書

徳島大学先端医療開発研究センター設置準備室成果報告書


尾部懸垂による筋肉内酸化ストレスと筋蛋白質のユビキチン化に対するシステインの阻害効果


Development of effective space food against weightlessness-induced muscle atrophy

The Progress Report of Ground Research Announcement for Space Utilization


Effects of space shuttle flight on gene expresson in rat skeletal muscle


微少重力環境下の骨格筋における蛋白質分解とプロテアーゼの発現

微少重力環境下の骨格筋における蛋白質分解とプロテアーゼの発現


重力により発現の変動する新規筋肉内遺伝子の解析

重力により発現の変動する新規筋肉内遺伝子の解析


無重力による筋萎縮に有効な宇宙食の開発

無重力による筋萎縮に有効な宇宙食の開発

宇宙環境利用に関する公募地上研究(平成10年度終了分)成果報告書

宇宙環境利用に関する公募地上研究(平成10年度終了分)成果報告書


新規アレルギー関連サイトカイン(IgE依存症ヒスタミン放出因子)産出に及ぼすM-CSFの役割


タンパク質必要量算定の現状と問題点

タンパク質必要量算定の現状と問題点


タンパク質栄養と熱ショック応答

タンパク質栄養と熱ショック応答


微小重力による筋萎縮とタンパク質分解酵素

微小重力による筋萎縮とタンパク質分解酵素


アニオン(O2-)の産生とその生理的役割

アニオン(O2-)の産生とその生理的役割


急性ストレス負荷時の胃粘膜におけるストレス蛋白質の誘導のメカニズムとその生理作用について


高脂肪食投与ラットの体脂肪蓄積に及ぼす大豆タンパク質と運動の効果

高脂肪食投与ラットの体脂肪蓄積に及ぼす大豆タンパク質と運動の効果


マクロファージコロニー刺激因子によるIgE依存症ヒスタミン放出因子の誘導

マクロファージコロニー刺激因子によるIgE依存症ヒスタミン放出因子の誘導


レドックス感受性転写因子NF-κBによる胃粘膜上皮細胞の酸化ストレス応答

レドックス感受性転写因子NF-κBによる胃粘膜上皮細胞の酸化ストレス応答


ラット腸粘膜IgA量に及ぼすタンパク質欠乏とコレラ毒素の影響

ラット腸粘膜IgA量に及ぼすタンパク質欠乏とコレラ毒素の影響


レチノイン酸による小腸上皮細胞株の分化誘導

レチノイン酸による小腸上皮細胞株の分化誘導


ストレスたん白質の誘導におよぼす大豆たん白質の影響

ストレスたん白質の誘導におよぼす大豆たん白質の影響


胃粘膜細胞のストレス反応の分子機構:グルタチオンによるストレス蛋白質遺伝子の転写調節について


運動に伴うフリーラジカル傷害の抑制に対する大豆たん白質の効果

運動に伴うフリーラジカル傷害の抑制に対する大豆たん白質の効果