title: The role of ZFP580, a novel zinc finger protein, in TGF-mediated cytoprotection against chemical hypoxia‑induced apoptosis in H9c2 cardiac myocytes.
abstract: Zing finger protein 580 (ZFP580) is a novel Cys2-His2 zinc-finger transcription factor that has an anti-apoptotic role in myocardial cells. It is involved in the endothelial transforming growth factor‑β1 (TGF‑β1) signal transduction pathway as a mothers against decapentaplegic homolog (Smad)2 binding partner. The aim of the present study was to determine the involvement of ZFP580 in TGF‑β1‑mediated cytoprotection against chemical hypoxia‑induced apoptosis, using H9c2 cardiac myocytes. Hypoxia was chemically induced in H9c2 myocardial cells by exposure to cobalt chloride (CoCl2). In response to hypoxia, cell viability was decreased, whereas the expression levels of hypoxia inducible factor-1α and ZFP580 were increased. Pretreatment with TGF‑β1 attenuated CoCl2‑induced cell apoptosis and upregulated ZFP580 protein expression; however, these effects could be suppressed by SB431542, an inhibitor of TGF‑β type I receptor and Smad2/3 phosphorylation. Furthermore, suppression of ZFP580 expression by RNA interference reduced the anti‑apoptotic effects of TGF‑β1 and thus increased CoCl2‑induced apoptosis. B‑cell lymphoma (Bcl)‑2‑associated X protein/Bcl‑2 ratio, reactive oxygen species generation and caspase‑3 activation were also increased following ZFP580 inactivation. In conclusion, these results indicate that ZFP580 is a component of the TGF-β1/Smad signaling pathway, and is involved in the protective effects of TGF‑β1 against chemical hypoxia‑induced cell apoptosis, through inhibition of the mitochondrial apoptotic pathway.
authors.affiliation: Sichuan Provincial Corps Hospital, Chinese People's Armed Police Forces, Leshan, Sichuan 614000, P.R. China.
authors.forename: Shi-Yun
authors.initials: SY
authors.lastname: Mao
authors.affiliation: Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, P.R. China.
authors.forename: Xiang-Yan
authors.initials: XY
authors.lastname: Meng
authors.affiliation: Central Laboratory, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, P.R. China.
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, P.R. China.
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Zhang
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Tianjin 300162, P.R. China.
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Jin
authors.affiliation: Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, P.R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Tianjin 300162, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Tianjin Key Laboratory of Cardiovascular Remodeling and Target Organ Injury, Pingjin Hospital Heart Center, Tianjin 300162, P.R. China.
authors.forename: Yu-Ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Tianjin Key Laboratory for Prevention and Control of Occupational and Environmental Hazard, Logistics University of Chinese People's Armed Police Force, Tianjin 300309, P.R. China.
authors.forename: Rui-Cheng
authors.initials: RC
authors.lastname: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity*; D019610:Cytoprotection; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D018125:Receptors, Transforming Growth Factor beta; D051899:Smad2 Protein; D051900:Smad3 Protein; C497787:Smad3 protein, rat; D014157:Transcription Factors; D053773:Transforming Growth Factor beta1; C000598274:ZFP580 protein, rat; D003035:Cobalt; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat; C018021:cobaltous chloride