title: Reduction of ribosome biogenesis with activation of the mTOR pathway in denervated atrophic muscle.
abstract: Mammalian target of rapamycin (mTOR) pathway positively regulates the cell growth through ribosome biogenesis in many cell type. In general, myostatin is understood to repress skeletal muscle hypertrophy through inhibition of mTOR pathway and myogenesis. However, these relationships have not been clarified in skeletal muscle undergoing atrophy. Here, we observed a significant decrease of skeletal muscle mass at 2 weeks after denervation. Unexpectedly, however, mTOR pathway and the expression of genes related to myogenesis were markedly increased, and that of myostatin was decreased. However, de novo ribosomal RNA synthesis and the levels of ribosomal RNAs were dramatically decreased in denervated muscle. These results indicate that ribosome biogenesis is strongly controlled by factors other than the mTOR pathway in denervated atrophic muscle. Finally, we assessed rRNA transcription factors expression and observed that TAFIa was the only factor decreased. TAFIa might be a one of the limiting factor for rRNA synthesis in denervated muscle.
authors.affiliation: Physical Education, Health and Sport Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Machida
authors.forename: Kohei
authors.initials: K
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yokono
authors.forename: Sachiko
authors.initials: S
authors.lastname: Ikemune
authors.forename: Yuka
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Kiyosawa
authors.forename: Tohru
authors.initials: T
authors.lastname: Takemasa
mesh_terms: D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009121:Muscle Denervation; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000473:pathology; D009133:Muscular Atrophy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D055435:Myostatin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012335:RNA, Ribosomal / Q000096:biosynthesis; D012270:Ribosomes / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: C525912:Mstn protein, mouse; D055435:Myostatin; D012333:RNA, Messenger; D012335:RNA, Ribosomal; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D018995:Myosin Heavy Chains