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Introduction: Diabetic neuropathy is a well-known complication of diabetes. Recently, hyperglycemia-induced toxicity has been confirmed to participates in multiple cellular pathways typical for neural deterioration. Nicotinamide phosphoribosyltransferase/pre-b cell colony-enhancing factor (Nampt/PBEF)/visfatin is a novel endogenous ligand that some studies have shown its neuroprotective effects on neurodegenerative disease. Therefore, we hypothesized that visfatin may prevent high glucose (HG)-induced neurotoxicity by inhibiting apoptosis, autophagy, and reactive oxygen species (ROS) responses properly. Methods: In this study, pheochromocytoma cell line 12 (PC12) cells were exposed to both HG concentrations (50, 75, 100, 125, 150 mM) and visfatin (50, 100, 150 ng/mL) at different time -points to determine the optimum time and dose of glucose and visfatin. To investigate the effects of visfatin on HG-induced damage in the PC12 diabetic neuropathy model, we examined ROS response, apoptosis, and autophagy using ROS detection kit, flow cytometry, and real-time PCR/Western blot, respectively. Results: We determined that HG concentration significantly increased the ROS level and apoptosis of diabetic PC12 cells. However, visfatin treatment significantly decreased the ROS production (P<0.05) and apoptosis of diabetic PC12 cells (P<0.0001). Beclin-1 messenger ribonucleic acid (mRNA) level (P<0.05) and light chain 3 (Lc3)-II protein level (P<0.05) showed that the autophagy pathway is impaired by HG concentrations. Conclusion: We concluded that visfatin can sufficiently decrease neural damage caused by ROS production and apoptosis under HG-induced toxicity. [ABSTRACT FROM AUTHOR]

• 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]

Methamphetamine (METH) is a potent psychomotor stimulant that has a high potential for abuse in humans. In addition, it is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to METH causes psychosis and increases the risk of Parkinson's disease. Apelin-13 is a novel endogenous ligand which studies have shown that may have a neuroprotective effect. Therefore, we hypothesized that Apelin-13 might adequately prevent METH-induced neurotoxicity via the inhibition of apoptotic, autophagy, and ROS responses. In this study, PC12 cells were exposed to both METH (0.5, 1, 2, 3, 4, 6 mmol/L) and Apelin-13 (0.5, 1.0, 2.0, 4.0, 8.0 μmol/L) in vitro for 24 h to measure determined dose, and then downstream pathways were measured to investigate apoptosis, autophagy, and ROS responses. The results have indicated that Apelin-13 decreased the apoptotic response post-METH exposure in PC12 cells by increasing cell viability, reducing apoptotic rates. In addition, the study has revealed Apelin-13 decreased gene expression of Beclin-1 by Real-Time PCR and LC3-II by western blotting in METH-induced PC12 cells, which demonstrated autophagy is reduced. In addition, this study has shown that Apelin-13 reduces intracellular ROS of METH-induced PC12 cells. These results support Apelin-13 to be investigated as a potential drug for treatment of neurodegenerative diseases. It is suggested that Apelin-13 is beneficial in reducing oxidative stress, which may also play an important role in the regulation of METH-triggered apoptotic response. Hence, these data indicate that Apelin-13 could potentially alleviate METH-induced neurotoxicity via the reduction of oxidative damages, apoptotic, and autophagy cell death. [ABSTRACT FROM AUTHOR]