Melatonin protects against apoptotic and autophagic cell death in C2C12 murine myoblast cells

Abstract

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.

Role of melatonin in the regulation of autophagy and mitophagy: A review

“…Numerous publications have confirmed the regulatory effect that melatonin has on apoptotic cell death and the antioxidant properties of melatonin in this process have been extensively investigated both in vivo and in vitro (Cagnoli et al, 1995;Sainz et al, 1995;Casado-Zapico et al, 2010;Leja-Szpak et al, 2010;Kim et al, 2011). Given that autophagy can culminate in programmed cell death type II, melatonin as a regulator of autophagy is currently under consideration (Kim et al, 2011).…”

“…Given that autophagy can culminate in programmed cell death type II, melatonin as a regulator of autophagy is currently under consideration (Kim et al, 2011). In numerous experimental and clinical situations, a beneficial effect of melatonin has been reported in different pathologies involving mitochondrial dysfunction which is usually accompanied by an increase in cellular ROS [and reactive nitrogen species (RNS)] which often culminate in cell death (León et al, 2004;Kanki, 2010;Acuña-Castroviejo et al, 2011).…”

Melatonin administration decreases adipogenesis in the liver of ob/ob mice through autophagy modulation

“…Numerous publications have confirmed the regulatory effects of melatonin on the cell cycle, triggering apoptosis in cancer cells that lead to cell death, and activation of autophagy as a survival mechanism . As both processes have been associated with obesity , increasing direct and indirect evidence suggests that melatonin is a potentially valuable target against excess weight gain.…”

Exosomes from Melatonin Treated Hepatocellularcarcinoma Cells Alter the Immunosupression Status through STAT3 Pathway in Macrophages

“…Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine that is synthesized and secreted primarily by the pineal gland, and has important functions, such as activating antioxidant enzymes, enhancing anti-aging properties 7-9, and possessing anti-tumor activities 8, 10-14. A large amount of evidence suggests that melatonin plays an important role in immunoregulation and anti-inflammatory responses 15.…”