ACE activity affects myogenic differentiation via mTOR signaling.
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.
Mori
Shuuichi
S
Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8574, Japan.
Tokuyama
Kumpei
K
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
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