Resveratrol Protects PC12 Cells from High Glucose-Induced Neurotoxicity Via PI3K/Akt/FoxO3a Pathway
Diabetes is known to be associated with neurodegenerative diseases. Resveratrol, a plant-derived polyphenolic compound found in red wine, possesses antioxidant properties. In this study, we aimed to investigate the effects of resveratrol on the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt)/FoxO3a pathway in mediating high glucose (HG)-induced injuries in neuronal PC12 cells. PC12 cells were exposed to HG to establish a model of HG neurotoxicity. Results showed that pre-treating PC12 cells with resveratrol before exposure to HG led to increased cell viability, decreased apoptotic cells, and reactive oxygen species generation. Western blot analysis showed that HG decreased the phosphorylation of Akt and FoxO3a and led to the nuclear localization of FoxO3a. These effects were significantly alleviated by resveratrol co-treatment. Furthermore, the protective effects of resveratrol were abolished by PI3K/Akt inhibitor LY294002. All these results demonstrate that resveratrol protected the PC12 cells from HG-induced oxidative stress and apoptosis via the activation of PI3K/Akt/FoxO3a signaling pathway.
KeywordsResveratrol High glucose Oxidative stress Apoptosis FoxO3a
This work was supported by grants from Medical scientific research funds of Guangdong Province (A2014810) and Graduate student research innovation project of Hunan Province (CX2013B397).
Conflict of interest
The authors have no conflict of interest.
- Wilk A, Urbanska K, Yang S, Wang JY, Amini S, Del Valle L, Peruzzi F, Meggs L, Reiss K (2011) Insulin-like growth factor-I-forkhead box O transcription factor 3a counteracts high glucose/tumor necrosis factor-alpha-mediated neuronal damage: implications for human immunodeficiency virus encephalitis. J Neurosci Res 89(2):183–198CrossRefPubMedCentralPubMedGoogle Scholar
- Wu PF, Xie N, Zhang JJ, Guan XL, Zhou J, Long LH, Li YL, Xiong QJ, Zeng JH, Wang F, Chen JG (2013) Resveratrol preconditioning increases methionine sulfoxide reductases A expression and enhances resistance of human neuroblastoma cells to neurotoxins. J Nutr Biochem 24(6):1070–1077CrossRefPubMedGoogle Scholar