Protective effect of melatonin on TNF‐α‐induced muscle atrophy in L6 myotubes

Abstract Muscle atrophy, characterized by decreased cell number and size, is a serious concern for patients afflicted with inflammatory diseases. Mounting evidence indicates that tumor necrosis factor alpha ( TNF ‐α) plays a critical role in muscle atrophy in a number of clinical settings. We hypothesize that reactive oxygen species ( ROS ) mediate TNF ‐α‐induced muscle cell death and hypotrophy. Recently, melatonin has attracted attention because of its free‐radical scavenging and antioxidant properties. The aim of the current study was to evaluate the possible protective role of melatonin in TNF ‐α‐induced muscle cell death and hypotrophy in rat L 6 myotubes. To examine this possible role, L 6 myotubes were exposed to various concentrations of recombinant TNF ‐α for 24 hr. We found that TNF ‐α at a concentration of 100 ng/mL induced ROS generation and decreased cell viability. Further analysis revealed that apoptosis, but not autophagy, may be important for TNF ‐α‐induced cell death. Melatonin significantly attenuated TNF ‐α‐induced ROS generation and apoptosis. In addition, decreased muscle fiber diameter and increased muscle cell proteolysis by TNF ‐α was highly attenuated by treatment with melatonin. The effects of melatonin were mediated neither through its plasmalemmal receptors nor by modulating the nuclear factor kappa B pathway activated by TNF ‐α. Taken together, these results suggest that TNF ‐α may mediate ROS ‐induced muscle cell death and hypotrophy and that melatonin may be a useful tool for protecting against muscle atrophy stemming from inflammatory diseases.