title: ACE activity affects myogenic differentiation via mTOR signaling.
abstract: Variation in ACE activity affects myogenic differentiation in C2C12 cells. The present study investigated the mechanism by which ACE influences the myogenic differentiation using the ACE-transduced C2C12 cells. Overexpression of ACE induced the down-regulation of myosin heavy chain, a late myogenic marker at 3-5 days after induction of differentiation. ACE-transduced cells exhibited the immature myotubes but an early myogenic marker (myogenin) was transiently increased at day 1. In ACE-transduced cells, phosphorylation of mTOR and its downstream effector (p70S6K) was suppressed at 2-5 day. However, upstream effector of mTOR (Akt) was transiently suppressed at day 3. Expression of IGF-II mRNA, which is controlled by mTOR, was also down-regulated during the differentiation in ACE-transduced cells. On the other hand, the treatment of cells with captopril, an ACE inhibitor, induced up-regulations of myosin heavy chain and phosphorylated p70S6K. These results suggest that ACE negatively regulates the myotube maturation via impairment of mTOR function.
authors: Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japan.
authors: Shuuichi
authors: S
authors: Mori
authors: Kumpei
authors: K
authors: Tokuyama
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002216:Captopril / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D015870:Gene Expression; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011494:Protein Kinases / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D014162:Transfection
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D012333:RNA, Messenger; D007335:Insulin-Like Growth Factor II; D002216:Captopril; D011494:Protein Kinases; C546842:MTOR protein, human; C546843:mTOR protein, mouse; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; D007703:Peptidyl-Dipeptidase A