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PREVENTIVE EFFECTS OF ANTIOXIDATIVE NUTRIENTS ON UNWEIGHTING-INDUCED PROTEIN UBIQUITINATION AND DEGRADATION IN RAT SKELETAL MUSCLE.  K. Hirasaka¹, M. Kano¹, M. Ikemoto¹, Y. Asanoma¹, T. Ogawa², K. Kishi¹ and T. Nikawa^{1  1}Dept of Nutrition and ²Dept of Orthopedic Surgery, School of Medicine, Univ of Tokushima.

                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 [FASEB J. 15 (2001) 1279-1281].  To elucidate whether the ubiquitination 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 protein ubiquitination, we administered antioxidative nutrients, cysteine and α-tocopherol, to tail-suspension rats.  Intragastric supplementation of 140 mg/rat of cysteine normalized the ratio of GSH to GSSG in the muscle and suppressed protein ubiquitination and MHC fragmentation, leading to the partial prevention of hindlimb muscle mass loss.  In contrast, supplementation of 15 mg/rat of α-tocopherol did not suppressed protein ubiquitination and MHC fragmentation possibly due to its prooxidant action. Our results suggest that supplementation of antioxidative nutrients, such as cysteine, may be beneficial for preventing ubiquitination of muscle proteins caused by microgravity.