ZFP580, a Novel Zinc-Finger Transcription Factor, Is Involved in Cardioprotection of Intermittent High-Altitude Hypoxia against Myocardial Ischemia-Reperfusion Injury

Abstract

BackgroundZFP580 is a novel C2H2 type zinc-finger transcription factor recently identified by our laboratory. We previously showed that ZFP580 may be involved in cell survival and growth. The aim of this study was to elucidate whether ZFP580 is involved in the cardioprotective effects of intermittent high-altitude (IHA) hypoxia against myocardial ischemia-reperfusion (I/R) injury.Methods and ResultsAfter rats were subjected to myocardial ischemia for 30 min followed by reperfusion, ZFP580 expression in the left ventricle was measured. ZFP580 protein expression was found to be up-regulated within 1 h and decreased at 2 h after reperfusion. Comparing normoxic and IHA hypoxia-adapted rats (5000 m, 6 h day−1, 6 weeks) following I/R injury (30 min ischemia and 2 h reperfusion), we found that adaptation to IHA hypoxia attenuated infarct size and plasma leakage of lactate dehydrogenase and creatine kinase-MB. In addition, ZFP580 expression in the myocardium was up-regulated by IHA hypoxia. Consistent with this result, ZFP580 expression was found to be significantly increased in cultured H9c2 myocardial cells in the hypoxic preconditioning group compared with those in the control group following simulated I/R injury (3 h simulated ischemic hypoxia and 2 h reoxygenation). To determine the role of ZFP580 in apoptosis, lentivirus-mediated gene transfection was performed in H9c2 cells 72 h prior to simulated I/R exposure. The results showed that ZFP580 overexpression significantly inhibited I/R-induced apoptosis and caspase-3 activation. H9c2 cells were pretreated with or without PD98059, an inhibitor of ERK1/2 phosphorylation, and Western blot results showed that PD98059 (10 µM) markedly suppressed I/R-induced up-regulation of ZFP580 expression.ConclusionsOur findings demonstrate that the cardioprotective effect of IHA hypoxia against I/R injury is mediated via ZFP580, a downstream target of ERK1/2 signaling with anti-apoptotic roles in myocardial cells.

Novel Zinc Finger Transcription Factor ZFP580 Facilitates All-Trans Retinoic Acid -Induced Vascular Smooth Muscle Cells Differentiation by Rarα-Mediated PI3K/Akt and ERK Signaling

“…Furthermore, it was also reported that ATRA activated SM22a expression through KLF4 binding to its ciselements in an acetylation-dependent manner and inhibited VSMC differentiation [14]. Our previous studies have shown that the novel zinc-finger transcription factor ZFP580 plays important roles in endothelial biology and cardiovascular disease [24][25][26]. We then evaluated the role of ZFP580 in VSMC biology using both gain-and loss-of-function analyses.…”

“…Bioinformatic analyses revealed that ZFP580 is also a C2H2 (Cys2-His2) zinc-finger protein that contains 172 amino acids, and 97% of the amino acid sequence is consistent with ZNF580. Our previous study has shown that ZFP580 had an anti-apoptotic effect on myocardial ischemia reperfusion injury [24]. The expression of ZFP580 significantly changed in VSMCs with intimal neovascularization.…”

Renalase Protects the Cardiomyocytes of Sprague-Dawley Rats Against Ischemia and Reperfusion Injury by Reducing Myocardial Cell Necrosis and Apoptosis

“…Thus, the reduction of cell necrosis and apoptosis are thought to be effective Li/Xie/Lin/Huang/Liang/Huang/Jiang: Renalase in Myocardial Ischemia Reperfusion Injury expression in SD rats [20][21][22][23][24][25][26]. We set the Left anterior descending coronary artery LAD) blocking time at 45 min and the reperfusion time at 4 h based on our previous preliminary experiment [27].…”

The role of ZFP580, a novel zinc finger protein, in TGF-mediated cytoprotection against chemical hypoxia-induced apoptosis in H9c2 cardiac myocytes

“…Our previous study indicated that ZNF580 is ubiquitously expressed in human tissues, and serves important roles in maintaining normal cell functions, including migration and proliferation (4,5). ZFP580 is the murine homologue of ZNF580, research regarding cloned ZFP580 (6) revealed that intermittent hypoxia could induce expression, which displayed an anti-apoptotic role during early phase ischemia-reperfusion injury (7). However, the mechanism and signaling pathways underlying the anti-apoptotic effects of ZFP580 have not yet been fully elucidated.…”