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CLINOROTATION PREVENTS DIFFERENTIATION OF RAT MYOBLASTIC CELLS IN ASSOCIATION WITH REDUCED IκB-UBIQUITINATION   K. Hirasaka¹, L. Yuge², I. Ishihara¹, M. Kano¹, Y. Asanoma¹, A. Okubo², T. Miyashita², T. Ogawa³, K. Kishi¹ and T. Nikawa^{1  1}Dept of Nutrition, Univ of Tokushima School of Medicine, Tokushima; ²Inst of Health Science, Faculty of Medicine, Hiroshima Univ, Hiroshima; ³Dept of Orthopaedics, Univ of Tokushima School of Medicine, Tokushima, JAPAN.

   In this study, we examined the effect of the three-dimensional (3D)-clinorotation, a simulated-model of microgravity, on the differentiation of rat myoblastic L6 cells. L6 cells subjected to the 3D-clinorotation did not differentiate into myotubes, although the 3D-clinorotaion had no effect on the proliferation. The 3D-clinorotation prevented expression of myogenin and myosin heavy chain (MHC) at the mRNA level. We found that the 3D-clinorotation inhibited the protein-ubiquitination in L6 cells. Thus, we focused on the ubiquitin-dependent degradation of a myogenesis inhibitory protein, IκB. The IκB protein level in L6 cells was constant during the rotation, whereas its protein level in the nonrotated cells decreased along with the differentiation. The 3D-clinorotation prevented the ubiquitination of IκB in the IκB- and ubiquitin-expressing Cos7 cells. A proteasome inhibitor, epoxomicin, prevented the differentiation of L6 cells in association with the inhibition of IκB degradation. Our results suggest that simulated microgravity such as the 3D-clinorotation prevents skeletal muscle cell differentiation by inhibiting the NF-κB signaling. The impaired muscle cell differentiation may lead to muscle atrophy during prolonged weightlessness.