| Author |
Yan, Yu-Feng Chen, He-Ping Xu, Qiang Qiu, Ling-Yu Liao, Zhang-Ping Yang, Wen-Jie Huang, Xiao-Shan Huang, Qi-Ren |
| Description |
Author Affiliation: Yan YF ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.); Yang WJ ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.); Xu Q ( Jiangxi Nursing Vocational and Technical College, Nanchang, Jiangxi 330006, P.R. China.); Chen HP ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.); Huang XS ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.); Qiu LY ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.); Liao ZP ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.); Huang QR ( Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.) |
| Abstract |
DJ-1 protein, as a multifunctional intracellular protein, has an important role in transcriptional regulation and anti-oxidant stress. A recent study by our group showed that DJ-1 can regulate the expression of certain antioxidant enzymes and attenuate hypoxia/reoxygenation (H/R)induced oxidative stress in the cardiomyocyte cell line H9c2; however, the detailed molecular mechanisms have remained to be elucidated. Nuclear factor erythroid 2like 2 (Nrf2) is an essential transcription factor that regulates the expression of several antioxidant genes via binding to the antioxidant response element (ARE). The present study investigated whether activation of the Nrf2 pathway is responsible for the induction of antioxidative enzymes by DJ1 and contributes to the protective functions of DJ1 against H/Rinduced oxidative stress in H9c2 cells. The results demonstrated that DJ1overexpressing H9c2 cells exhibited antioxidant enzymes, including manganese superoxide dismutase, catalase and glutathione peroxidase, to a greater extent and were more resistant to H/Rinduced oxidative stress compared with native cells, whereas DJ1 knockdown suppressed the induction of these enzymes and further augmented the oxidative stress injury. Determination of the importance of Nrf2 in DJ1mediated antioxidant enzymes induction and cytoprotection against oxidative stress induced by H/R showed that overexpression of DJ1 promoted the dissociation of Nrf2 from its cytoplasmic inhibitor Keap1, resulting in enhanced levels of nuclear translocation, AREbinding and transcriptional activity of Nrf2. Of note, Nrf2 knockdown abolished the DJ1mediated induction of antioxidant enzymes and cytoprotection against oxidative stress induced by H/R. In conclusion, these findings indicated that activation of the Nrf2 pathway is a critical mechanism by which DJ-1 upregulates anti-oxidative enzymes and attenuates H/R-induced oxidative stress in H9c2 cells. |
