| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2006: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 2005: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
Porcine Stress Syndrome (PSS) is caused by a combined genetic and environmental factor. In generally PSS pig exhibits the pale, soft and exudative meat in which cellular proteolytic systems are induced and activated resulting in accelerated proteolysis. The purpose of this study was to clarify the cellular and molecular mechanism of the muscle abnormality caused by stress hormone, glucocorticoid. [EXP 1] mRNA expression of atrogin-1, a muscle atrophy specific ubiquitin ligase, was investigated in the atrophying muscles from pigs treated with catabolic dose of cortisol (10 or 30 mg/kg/BW). The mRNA expressions of atrogin-1 and GAPDH as an internal marker gene were determined by the real-time quantitative PCR method. Unexpectedly, atrogin-1 mRNA expression was decreased in response to cortisol administration in a dose dependent manner. [EXP 2] Effects of dexamethasone (Dex), insulin-like growth factor 1 (IGF-1), and testosterone on mRNA expression of atrogin-1 in C2C12 myotubes were examined. Dex markedly increased the atrogin-1 expression (7-8-fold of control), on the other hand, IGF-1 and testosterone slightly reduced the increased expression. The rate of protein breakdown evaluated by the release of 3-methlyhisitidine as an index of myofibrillar degradation was significantly increased in the presence of Dex, but not changed in the presence of both of Dex and IGF-1. [EXP 3] Changes in cellular ultrastructure of the mouse muscle atrophies induced by Dex administration (1mg/kgBW/day) or 48h-fasting were investigated by using transmission electron microscope (TEM) and immune TEM with gold-conjugate secondary antibody. The myofibrillar structure was brittle, and the amount of desmin, a structural protein in the M-filament of myofibril, was reduced in the atrophying muscles. These results suggest that argoin-1 plays an important role in the initiation and progression of the muscle atrophies, and IGF-1 is could be used for the treatment of muscle atrophies.
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