Abstract
Oxidative stress has been suggested to play an important role in neuronal injury. Ethyl gallate (EG) is the ethyl ester of gallic acid which has been acknowledged as an antioxidant. We previously demonstrated that EG effectively inhibited H2O2-induced cytotoxicity and decreased the ROS levels in PC12 cells, while the relevant mechanisms of action of this compound remain largely uncharacterized. The present study was carried out in an attempt to clarify the underlying mechanisms of EG against H2O2-induced neurotoxicity in PC12 cells. EG pretreatment attenuated H2O2-induced mitochondrial dysfunction as indicated by the decreased caspase-9/−3 activation, PARP cleavage, mitochondrial membrane potential (MMP) depletion, Bax/Bcl-2 ratio, cytochrome c release and ROS overproduction. Furthermore, EG treatment resulted in nuclear translocation of Nrf2 along with increased expression of ARE-dependent cytoprotective genes, such as γ-GCS and NQO1, which indicated EG as an Nrf2 pathway activator. Silencing of Nrf2 signaling by siRNA abrogated the protective effects offered by EG on H2O2-induced PC12 cells injury, which suggested the important role of Nrf2 pathway in the protection of EG against oxidative stress induced PC12 cell apoptosis. These results taken together indicated that EG protects PC12 cells against H2O2-induced cell mitochondrial dysfunction possibly through activation of Nrf2 pathway. EG might be a potential candidate for further preclinical study aimed at the prevention and treatment of neurodegenerative diseases.
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Acknowledgments
This work was funded by the Key Research and Development Program of Shandong Province (grant number 2018GSF118085 and 2017GSF218049); Shandong Provincial Natural Science Foundation (grant number 2015ZRE27209) and National Natural Science Foundation of China (grant number 81673558).
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Chen, L., Wu, X., Shen, T. et al. Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells. Metab Brain Dis 34, 545–555 (2019). https://doi.org/10.1007/s11011-019-0382-z
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DOI: https://doi.org/10.1007/s11011-019-0382-z