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Skeletal muscle gene expression in healthy volunteers with a 20-day-bed-rest.    H. Furochi, T. Ogawa, M. Mameoka, K. Hirasaka, N. Yasui, K. Kishi, T. Nikawa.  The University of Tokushima School of Medicine, Tokushima, Japan

   In experimental animal models, several ubiquitin ligases, such as MuRF-1 and atrogin-1, play an important role in skeletal muscle atrophy caused by unloading.  In this study, to find ubiquitin ligases involved in muscle atrophy of human beings, we comprehensively examined gene expression in skeletal muscles prepared from healthy volunteers with a 20-day-bed-rest. During 20-day-bed rest, thickness and sectional area of quadriceps femoris muscle significantly decreased by 4.6% and 3.7%, respectively.  In addition, ubiquitinated proteins were accumulated in these atrophied human muscles. DNA microarray analysis showed that a bed-rest preferentially suppressed gene transcription in skeletal muscle: the number of genes that exhibited more than a 2-fold significant change in expression level was 83 (Up, 4 genes; Down, 79 genes).  Nevertheless transcriptional activities were inhibited in muscle, real-time reverse transcription and polymerase chain reaction showed that the bed-rest significantly up-regulated expression of 2 ubiquitin-ligase genes, Cbl-b and atrogin-1.  Our present results suggest that in human beings, the ubiquitin-dependent proteolytic pathway plays an important role in unloading-induced muscle atrophy, and that these up-regulated ubiquitin ligases may mediate ubiquitination of muscle proteins.

   (This work was supported by the Grants-in aid of “Ground Research Announcement for Space Utilization” promoted by Japan Aerospace Exploration Agency and Japan Space Forum to T. N. and H. F.)