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SPACE SHUTTLE FLIGHT (STS-90) ENHANCES DEGRADATION OF RAT MYOSIN HEAVY CHAIN IN ASSOCIATION WITH ACTIVATION OF UBIQUITIN-PROTEASOME PATHWAY M. Ikemoto¹, T. Nikawa¹, S. Takeda², C. Watanabe¹, T. Kitano¹, K. M. Baldwin³, R. Izumi⁴, I. Nonaka⁵, T. Towatari⁶, S. Teshima¹, K. Rokutan¹ and K. Kishi^{1 1}The University of Tokushima;  ²National Center of Neurology and Psychiatry;  ³University of California Irvine;  ⁴National Space Development Agency of Japan;  ⁵National Center of Neurology and Psychiatry;  ⁶University of Tokushima.

     To elucidate the mechanisms of microgravity-induced muscle atrophy, we focused on fast-type myosin heavy chain (MHC) degradation and expression of proteases in atrophied gastrocnemius muscles of neonatal rats exposed to 16-day spaceflight (STS-90).  The spaceflight stimulated ubiquitination of proteins, including a MHC molecule, and accumulation of MHC degradation fragments in the muscles.  Semi-quantitative reverse transcriptase-polymerase chain reaction revealed that the spaceflight significantly increased mRNA levels of cathepsin L, proteasome components (RC2 and RC9), polyubiquitin and ubiquitin-conjugating enzyme in the muscles, compared with those of ground control rats.  The levels of m-calpain, m-calpain, cathepsin B and cathepsin H mRNAs were not changed by the spaceflight.  We also found that tail-suspension of rats for 10 days or longer caused the ubiquitination and degradation of MHC in gastrocnemius muscle, as was observed in the spaceflight rats.  In the muscle of suspended rats, these changes were closely associated with activation of proteasome and up-regulation of expression of mRNA for the proteasome components and polyubiquitin.  Administration of a cysteine protease inhibitor, E-64, to the suspended rats did not prevent the MHC degradation.  Our results suggest that spaceflight induces the degradation of muscle contractile proteins including MHC, possibly through a ubiquitin-dependent proteolytic pathway.