Involvement of p38 MAPK-mediated signaling in the calpeptin-mediated suppression of myogenic differentiation and fusion in C2C12 cells.
Calpeptin inhibits myoblast fusion by inhibiting the activity of calpain. However, the mechanism by which calpeptin inhibits myogenesis is not completely understood. This study examined how calpeptin affects the expression of the myogenic regulatory factors (MRFs) and the phosphorylation of p38 mitogen-activated protein kinase (MAPK) in differentiating C2C12 myoblasts. Consistent with previous reports, calpeptin inhibited the induction of mu-calpain and the formation of myotubes in these cells. In particular, calpeptin inhibited the expression of the early and mid differentiation markers including MyoD, Myf5, myogenin, and MRF4 as well as the expression of the late markers such as troponin T and myosin heavy chain (MyHC). Calpeptin also suppressed the phosphorylation of p38 MAPK in C2C12 cells. SB203580, a specific p38 inhibitor, prevented the expression of the muscle-specific markers and their fusion into myotubes in these cells, which was further accelerated in the presence of calpeptin. These findings suggest that calpeptin inhibits the myogenesis of skeletal muscle cells by down-regulating the MRFs and involving p38 MAPK signaling.
Division of Biological Sciences, Chonbuk National University, Chonju 561-756, Korea.
Sung-Ho
SH
Kook
Ki-Choon
KC
Choi
Young-Ok
YO
Son
Kyung-Yeol
KY
Lee
In-Ho
IH
Hwang
Hyun-Jeong
HJ
Lee
Wan-Tae
WT
Chung
Choon-Bong
CB
Lee
Jong-Sun
JS
Park
Jeong-Chae
JC
Lee
D000818:Animals; D002154:Calpain / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002459:Cell Fusion; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D024510:Muscle Development / Q000187:drug effects*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D017570:MyoD Protein / Q000378:metabolism; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D018006:Myogenic Regulatory Factors / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000378:metabolism; D020107:Troponin T / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D050759:Cyclin-Dependent Kinase Inhibitor p21; D004151:Dipeptides; D017570:MyoD Protein; D018006:Myogenic Regulatory Factors; D020107:Troponin T; C071482:calpeptin; D048051:p38 Mitogen-Activated Protein Kinases; D002154:Calpain; C449002:mu-calpain; D018995:Myosin Heavy Chains