title: DJ-1 upregulates anti-oxidant enzymes and attenuates hypoxia/re-oxygenation-induced oxidative stress by activation of the nuclear factor erythroid 2-like 2 signaling pathway.
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 anti‑oxidant enzymes and attenuate hypoxia/re‑oxygenation (H/R)‑induced oxidative stress in the cardiomyocyte cell line H9c2; however, the detailed molecular mechanisms have remained to be elucidated. Nuclear factor erythroid 2‑like 2 (Nrf2) is an essential transcription factor that regulates the expression of several anti‑oxidant genes via binding to the anti‑oxidant response element (ARE). The present study investigated whether activation of the Nrf2 pathway is responsible for the induction of anti‑oxidative enzymes by DJ‑1 and contributes to the protective functions of DJ‑1 against H/R‑induced oxidative stress in H9c2 cells. The results demonstrated that DJ‑1‑overexpressing H9c2 cells exhibited anti‑oxidant enzymes, including manganese superoxide dismutase, catalase and glutathione peroxidase, to a greater extent and were more resistant to H/R‑induced oxidative stress compared with native cells, whereas DJ‑1 knockdown suppressed the induction of these enzymes and further augmented the oxidative stress injury. Determination of the importance of Nrf2 in DJ‑1‑mediated anti‑oxidant enzymes induction and cytoprotection against oxidative stress induced by H/R showed that overexpression of DJ‑1 promoted the dissociation of Nrf2 from its cytoplasmic inhibitor Keap1, resulting in enhanced levels of nuclear translocation, ARE‑binding and transcriptional activity of Nrf2. Of note, Nrf2 knockdown abolished the DJ‑1‑mediated induction of anti‑oxidant 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.
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Yu-Feng
authors.initials: YF
authors.lastname: Yan
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Jiangxi Nursing Vocational and Technical College, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Xu
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: He-Ping
authors.initials: HP
authors.lastname: Chen
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiao-Shan
authors.initials: XS
authors.lastname: Huang
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Qiu
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Zhang-Ping
authors.initials: ZP
authors.lastname: Liao
authors.affiliation: Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qi-Ren
authors.initials: QR
authors.lastname: Huang
mesh_terms: D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D004790:Enzyme Induction; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress; D000071617:Protein Deglycase DJ-1; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1