Resveratrol Suppresses Rotenone‐induced Neurotoxicity Through Activation of SIRT1/Akt1 Signaling Pathway

Citations Over TimeTop 10% of 2018 papers

Abstract

Rotenone is a common pesticide and has been reported as one of the risk factors for Parkinson disease. Rotenone can cause neuronal death or apoptosis through inducing oxidative injury and inhibiting mitochondrial function. As a natural polyphenolic compound, resveratrol possesses the antioxidant capacity and neuroprotective effect. However, the mechanism underlying the neuroprotective effect of resveratrol against rotenone-induced neurotoxicity remains elusive. Here, we treated PC12 cells with rotenone to induce neurotoxicity, and the neurotoxic cells were subjected to resveratrol treatment. The CCK8 and LDH activity assays demonstrated that resveratrol could suppress neurotoxicity induced by rotenone (P < 0.01). The DCFH-DA assay indicated that resveratrol reduced the production of reactive oxygen species (ROS). JC-1 and Hoechst 33342/PI staining revealed that resveratrol attenuated mitochondrial dysfunction and cell apoptosis. Moreover, resveratrol reversed rotenone-induced decrease in SIRT1 expression and Akt1 phosphorylation (P < 0.05). Furthermore, when the SIRT1 and Akt1 activity was inhibited by niacinamide and LY294002, respectively, the neuroprotective effect of resveratrol was remarkably attenuated, which implied that SIRT1 and Akt1 could mediate this process and may be potential molecular targets for intervening rotenone-induced neurotoxicity. In summary, our study demonstrated that resveratrol reduced rotenone-induced oxidative damage, which was partly mediated through activation of the SIRT1/Akt1 signaling pathway. Our study launched a promising avenue for the potential application of resveratrol as a neuroprotective therapeutic agent in Parkinson disease. Anat Rec, 301:1115-1125, 2018. © 2018 Wiley Periodicals, Inc.

Related Papers

• → Red Wine Ingredient Resveratrol Protects from β-Amyloid Neurotoxicity(2003)180 cited
• → PACAP protects neuronal differentiated PC12 cells against the neurotoxicity induced by a mitochondrial complex I inhibitor, rotenone(2005)82 cited
• → Resveratrol Protects Cortical Neurons against Microglia‐mediated Neuroinflammation(2012)76 cited
• → Neuroprotective effect of resveratrol on rotenone-treated C57BL/6 mice(2017)20 cited
• → Neuroprotective effects of tomato seed extract against rotenone-induced oxidative impairments and neurotoxicity in mice(2013)6 cited