Development of novel nutritional methods to inhibit muscle atrophy caused by microgravity.

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We have previously reported that spaceflight and tail suspension enhanced degradation of rat myosin heavy chain (MHC) in association with activation of a ubiquitin-dependent proteolytic pathway. In the serial study, about 26,000 gastrocnemius muscle gene expression in rats exposed to the spaceflight or tail-suspension was accessed by DNA microarray analysis, and we found that gene expression in the ubiquitin-dependent proteolysis in these rats was up-regulated. In the present study, to elucidate whether the altered gene expression is accompanied by oxidative stress, we measured markers for oxidative stress, such as thiobarbituric acid ?reactive substance (TBARS), glutathione disulfide (GSSG), and glutathione (GSH), in gastrocnemius muscle of tail-suspended rat. Tail-suspension reciprocally increased concentration of TBARS and GSSG in parallel with enhancement of protein ubiquitination, suggesting that oxidative stress may play an important role in protein ubiquitination caused by tail-suspension. To prevent ubiquitination associated with oxidative stress, we also administered an antioxidative nutrient, cysteine and vitamin E, to tail-suspension rats. Intragastric supplementation of 140 mg/rat of cysteine for 2 weeks or longer normalized the ratio of GSH to GSSG in the muscle and suppressed protein ubiquitination and MHC fragmentation, compared with supplementation of the equimolar amount of alanine. The cysteine supplementation significantly suppressed the loss of hindlimb muscle mass. Not only supplementation of 15 mg/rat of α-tocopherol did not suppressed protein ubiquitination and MHC fragmentation, but also loss of hindlimb muscle mass. Our results suggest that effect of antioxidative nutrients depend on supplement amount and may be beneficial for preventing ubiquitination of muscle proteins caused by unweighting.