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Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells.
Metab Brain Dis. 2019 04; 34(2):545-555.MB

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.

Authors+Show Affiliations

Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China.Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44 Wenhuaxi Road, Jinan, 250012, People's Republic of China. rendom@sdu.edu.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30746596

Citation

Chen, Lan, et al. "Protective Effects of Ethyl Gallate On H2O2-induced Mitochondrial Dysfunction in PC12 Cells." Metabolic Brain Disease, vol. 34, no. 2, 2019, pp. 545-555.
Chen L, Wu X, Shen T, et al. Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells. Metab Brain Dis. 2019;34(2):545-555.
Chen, L., Wu, X., Shen, T., Wang, X., Wang, S., Wang, J., & Ren, D. (2019). Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells. Metabolic Brain Disease, 34(2), 545-555. https://doi.org/10.1007/s11011-019-0382-z
Chen L, et al. Protective Effects of Ethyl Gallate On H2O2-induced Mitochondrial Dysfunction in PC12 Cells. Metab Brain Dis. 2019;34(2):545-555. PubMed PMID: 30746596.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells. AU - Chen,Lan, AU - Wu,Xuewei, AU - Shen,Tao, AU - Wang,Xiaoning, AU - Wang,Shuqi, AU - Wang,Jinxia, AU - Ren,Dongmei, Y1 - 2019/02/12/ PY - 2018/05/31/received PY - 2019/01/03/accepted PY - 2019/2/13/pubmed PY - 2019/8/14/medline PY - 2019/2/13/entrez KW - Ethyl gallate KW - Mitochondrial dysfunction KW - Nrf2 pathway KW - PC12 cells SP - 545 EP - 555 JF - Metabolic brain disease JO - Metab Brain Dis VL - 34 IS - 2 N2 - 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. SN - 1573-7365 UR - https://www.unboundmedicine.com/medline/citation/30746596/Protective_effects_of_ethyl_gallate_on_H2O2_induced_mitochondrial_dysfunction_in_PC12_cells_ L2 - https://doi.org/10.1007/s11011-019-0382-z DB - PRIME DP - Unbound Medicine ER -