Muscular cell proliferative and protective effects of N-acetylcysteine by modulating activity of extracellular signal-regulated protein kinase.
N-acetylcysteine (NAC), an antioxidant and a precursor of glutathione, is currently in clinical use for various pathological conditions. No data is available as to the relationship between NAC and muscular cell proliferation or muscular degenerative disease. In this study, we assessed the effect of NAC on growth of L6 myoblasts, a rat skeletal muscle cell line, under normal or bupivacaine-treated condition. Of interest, under normal growth conditions, NAC treatment concentration-dependently increased viability, cell number, and DNA incorporation of L6 cells. Remarkably, NAC treatment for 12 to 24 h led to increased phosphorylation of ERKs, a family of mitogen-activated protein kinase known to involve in cell proliferation, in L6 cells, and specific inhibition of ERKs by PD98059, a selective inhibitor of ERKs, greatly abolished the ability of NAC to increase the number of L6 cells. More importantly, pretreatment with NAC effectively blocked decrease in the number and ERKs phosphorylation in L6 cells induced by the exposure of bupivacaine, a local anesthetic with myotoxicity. These results collectively suggest that NAC has muscular cell proliferative and protective effects and the effects by NAC appear to be, in part, mediated via increase in ERKs activation.
Department of Neurology, Keimyung University School of Medicine and Institute for Medical Science, 194 Dongsan-Dong, Jung-Gu, Daegu 700-712, Korea.
Geun-Ho
GH
Kim
Dae-Kyu
DK
Song
Chi-Heum
CH
Cho
Sun Kyun
SK
Yoo
Dae-Kwang
DK
Kim
Gi-Young
GY
Park
Seong-il
SI
Suh
Byeong-Churl
BC
Jang
Jeong-Geun
JG
Lim
D000111:Acetylcysteine / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000963:Antimetabolites; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D001973:Bromodeoxyuridine; D002045:Bupivacaine / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D032342:Muscle Cells / Q000187:drug effects; D018482:Muscle, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000187:drug effects; D012038:Regeneration / Q000187:drug effects
D000779:Anesthetics, Local; D000963:Antimetabolites; D000975:Antioxidants; D048049:Extracellular Signal-Regulated MAP Kinases; D001973:Bromodeoxyuridine; D000111:Acetylcysteine; D002045:Bupivacaine