| Project/Area Number |
11670071
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Environmental physiology (including Physical medicine and Nutritional physiology)
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| Research Institution | The University of Tokushima |
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Principal Investigator |
KISHI Kyoichi The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (80035435)
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| Co-Investigator(Kenkyū-buntansha) |
TESHIMA Shigetada The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 助手 (40304513)
NIKAWA Takeshi The University of Tokushima, School of Medicine, Assistant Professor, 医学部, 助手 (20263824)
ROKUTAN Kazuhito The University of Tokushima, School of Medicine, Associate Professor, 医学部, 助教授 (10230898)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | disuse-induced muscle atrophy / cathepsin / calpain / proteasome / cysteine supplementation / mitochondrial gene |
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| Research Abstract |
To elucidate the mechanisms of microgravity-induced muscle atrophy, we focused on myosin heavy chain (MHC) degradation and gene expression in atrophied gastrocnemius muscles of neonatal rats exposed to 16-day spaceflight. The spaceflight stimulated ubiquitination of proteins, including a MHC molecule, and accumulation of MHC degradation fragments in the muscles. The spaceflight significantly increased mRNA levels of cathepsin L, proteasome components (RC2 and RC9), polyubiquitin, ubiquitin-conjugating enzyme, NADH dehydrogenase and 16S ribosome RNA in the muscles, compared with those of ground control rats. The levels of μ-calpain, m-calpain, cathepsin B and cathepsin H mRNAs were not changed by the spaceflight. Tail-suspension of rats for 10 days or longer also caused similar changes, as was observed in the spaceflight rats, suggesting that MHC degradation were closely associated with activation of proteasome-dependent proteolysis and abnormal expression of mitochondrial gene. We then tried to improve the suspension-induced muscle atrophy by amino acid supplementation. Intragastric supplementation of 140 mg of cysteine to suspended rats significantly prevented loss of the hindlimb muscle weight by suppressing ubiquitination of muscle protein. Adminstraton of glutamine, alanine or cysteine protease inhibitor had little effect on the atrophy. Cysteine may scavenge reactive oxygen radicals produced from mitochondria so that cysteine supplementation prevented suspension-induced ubiquitination of muscle protein.
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