Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) alleviates myocardial hypoxia-reoxygenation injury by inhibiting oxidative stress and ameliorating mitochondrial dysfunction

• Published in: Experimental and therapeutic medicine 2019-03, Vol.17 (3), p.2143-2151
• Main Authors: Hao, Jie, Du, Hong, Liu, Fan, Lu, Jing-Chao, Yang, Xiu-Chun, Cui, Wei
• Format: Article
• Language: English
• Subjects: Apoptosis; Biotechnology; Cardiomyocytes; Care and treatment; Cellular proteins; Cloning; Cytochrome; Cytochrome c; Cytochrome oxidase; Deoxyribonucleic acid; Development and progression; Disease; DNA; DNA damage; Enzymes; Genetic aspects; Health aspects; Hypoxia; Ischemia; Kinases; Lymphomas; Myocardial ischemia; Oxidases; Oxidative stress; Polyclonal antibodies; Proteins; Reactive oxygen species; Reperfusion injury; Studies; Superoxides; Tumors
• ISSN: 1792-0981; 1792-1015
• DOI: 10.3892/etm.2019.7212

Oxidative stress and mitochondrial dysfunction are considered to be activators of apoptosis and serve a pivotal role in the pathogenesis of myocardial ischemia-reperfusion (MI/R) injury. Apurinic/apyrimidinic endonuclease/redox factor 1 (APE1) is a multifunctional protein that processes the cellular response to DNA damage and oxidative stress. Little is known about the role of APE1 in the pathogenesis of MI/R injury. The aim of the present study was to investigate the effects of APE1 on hypoxia-reoxygenation (H/R)-induced H9c2 cardiomyocyte injury and the underlying mechanism responsible. It was demonstrated that H/R decreased cell viability and increased lactic dehydrogenase (LDH) release, as well as reducing APE1 expression in H9c2 cells. However, APE1 overexpression induced by transfection with APE1-expressing lentivirus significantly increased H9c2 cell viability, decreased LDH release, decreased apoptosis and reduced caspase-3 activity in H/R-treated H9c2 cells. APE1 overexpression ameliorated the H/R-induced increases in reactive oxygen species and NAPDH oxidase expression, as well as the decreases in superoxide dismutase activity and glutathione expression. Furthermore, APE1 overexpression increased mitochondrial membrane potential and ATP production, stabilized electron transport chain activity (as illustrated by increased NADH-ubiquinone oxidoreductase, succinate dehydrogenase, coenzyme Q-cytochrome c oxidoreductase and cytochrome c oxidase activities) and decreased the ratio of B-cell lymphoma 2-associated X protein/B-cell lymphoma 2 in H/R, improving mitochondrial dysfunction. In conclusion, the results of the present study suggest that APE1 alleviates H/R-induced injury in H9c2 cells by attenuating oxidative stress and ameliorating mitochondrial dysfunction. APE1 may therefore be used as an effective treatment for MI/R injury.