Involvement of p38 MAPK-mediated signaling in the calpeptin-mediated suppression of myogenic differentiation and fusion in C2C12 cells |
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Authors: | Sung-Ho Kook Ki-Choon Choi Young-Ok Son Kyung-Yeol Lee In-Ho Hwang Hyun-Jeong Lee Wan-Tae Chung Choon-Bong Lee Jong-Sun Park Jeong-Chae Lee |
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Institution: | (1) Division of Biological Sciences, Chonbuk National University, Chonju, 561-756, Korea;(2) Institute of Oral Biosciences, Chonbuk National University, Chonju, 561-756, Korea;(3) Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Korea University, Seoul, 152-050, Korea;(4) Research Center of Bioactive Materials, Chonbuk National University, Chonju, 561-756, Korea;(5) Department of Animal Resources and Biotechnology, Chonbuk National University, Chonju, 561-756, Korea;(6) National Livestock Research Institute, RDA, Suweon, 441-706, Korea |
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Abstract: | 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 μ-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. |
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Keywords: | C2C12 skeletal muscle cells Myogenesis Calpeptin p38 MAPK |
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