Nesfatin-1 protects PC12 cells against high glucose-induced cytotoxicity via inhibiting oxidative stress, autophagy and apoptosis.

• Nesfatin-1 reduces intracellular ROS in PC12 cells following glucose-induced neurotoxicity. • Nesfatin-1 reduces apoptosis of PC12 cells following glucose-induced neurotoxicity. • Nesfatin-1 reduces autophagy of PC12 cells following glucose-induced neurotoxicity. Diabetic neuropathy (DN) is the most common complication of diabetes mellitus. It is thought that neuronal cell death which is mainly due to reactive oxygen species (ROS) overproduction in the cells is responsible for most symptoms of this disorder. Nesfatin-1 has identified recently as a novel endogenous neuropeptide which recent studies have shown that it may have a protective effect. Therefore, we postulated that Nesfatin-1 might adequately prevent from high glucose-induced cell injury via inhibition of apoptotic, autophagy, and ROS responses. In this study, PC12 cells were pretreated with different concentrations of Nesfatin-1 (1–100 ng/ml) and then co-treated with Nesfatin-1 and glucose (125 mM) for 48 h, and downstream pathways then were evaluated to investigate ROS, apoptosis, and autophagy. Results of this study showed that Nesfatin-1 can not only inhibit from intracellular ROS overproduction-induced by high glucose in PC12 cells (p < 0.0001) but also reduce the apoptotic cell death in PC12 cells following high glucose exposure by increasing cell viability and reducing apoptotic rates (p < 0.05). Furthermore, Nesfatin-1 decreased the LC3-II levels by western blotting (p < 0.0001), which showed a reduction in autophagy. These results support the idea that Nasfatin-1can protect PC12 cells against high glucose-induced cell injury by inhibition of apoptosis, autophagy and ROS production and can be considered as a potential drug for treatment of diabetic neuropathy. [ABSTRACT FROM AUTHOR]