Melatonin protects against apoptotic and autophagic cell death in C2C12 murine myoblast cells.
In this study, we investigated whether or not melatonin inhibits apoptotic and autophagic cell death in C2C12 murine myoblast cells. Treatment of cells with S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, was shown to induce cell death, and treatment with melatonin (100 μm) significantly attenuated the occurrence of NO-induced cell death. Decreased p-Akt expression in response to NO was also arrested by melatonin. Under these conditions, p-Bad (Ser 136) expression increased with melatonin treatment prior to NO treatment. Treatment with Akt inhibitors (LY 294002, wortmannin) plus melatonin reduced p-Akt expression. Compared with NO treatment, Bcl-2 expression increased with melatonin treatment, while Bax expression was inhibited by melatonin treatment. Expression of catalase and Mn-superoxide dismutase (SOD) was elevated with melatonin treatment, whereas Cu/Zn-SOD expression decreased with melatonin, lower than NO treatment, respectively. Next, we investigated the question of whether or not melatonin may restrain autophagic cell death in C2C12 cells. Nutrient starvation induced a rise in expression of the microtubule-associated protein 1 light chain 3 (LC3)-II; however, melatonin treatment suppressed LC3-II expression by nutrient deprivation. Expression of Bcl-2, Bax, catalase, and Cu/Zn-SODs coincided with results of apoptotic cell death. Together, these results suggest that melatonin protects against apoptotic and autophagic cell death through the common pathway resulted in the increment of Bcl-2 expression and the reduction of Bax expression in C2C12 murine myoblast cells.
Department of Biomedical Engineering, College of Health Science, Yonsei University, Wonju, Gangwon-do, Korea.
Chi Hyun
CH
Kim
Kyung Hwan
KH
Kim
Yeong-Min
YM
Yoo
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D008550:Melatonin / Q000494:pharmacology*; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D026423:S-Nitroso-N-Acetylpenicillamine; D013482:Superoxide Dismutase; D051057:Proto-Oncogene Proteins c-akt; D008550:Melatonin; D000077191:Wortmannin