标题：Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells
作者：Chen, Lan; Wu, Xuewei; Shen, Tao; Wang, Xiaoning; Wang, Shuqi; Wang, Jinxia; Ren, Dongmei
作者机构：[Chen, Lan; Wu, Xuewei; Shen, Tao; Wang, Xiaoning; Wang, Shuqi; Wang, Jinxia; Ren, Dongmei] Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Ch 更多
通讯作者地址：[Ren, DM]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Key Lab Chem Biol, 44 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China.
来源：METABOLIC BRAIN DISEASE
关键词：Ethyl gallate; Mitochondrial dysfunction; Nrf2 pathway; PC12 cells
摘要：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 -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.