ZFP580, a novel zinc-finger transcription factor, is involved in cardioprotection of intermittent high-altitude hypoxia against myocardial ischemia-reperfusion injury.
ZFP580, a novel zinc-finger transcription factor, is involved in cardioprotection of intermittent high-altitude hypoxia against myocardial ischemia-reperfusion injury.
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新型锌指转录因子ZFP580参与间歇性高原缺氧对心肌缺血再灌注损伤的心脏保护作用
DOI：
10.1371/journal.pone.0094635
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Xu RC
中科院分区：
文献类型：
--
作者：
Meng XY;Yu HL;Zhang WC;Wang TH;Mai X;Liu HT;Xu RC
ZFP 580是本实验室新近发现的一种C2 H2型锌指转录因子。我们先前表明ZFP 580可能参与细胞存活和生长。本研究的目的是阐明ZFP 580是否参与了间歇性高原缺氧（IHA）对心肌缺血-再灌注（I/R）损伤的保护作用。大鼠心肌缺血30 min再灌注后，测定左心室ZFP 580的表达。ZFP 580蛋白表达在再灌注后1 h内上调，2 h下降。比较I/R损伤（30 min缺血和2 h再灌注）后常氧和IHA低氧适应大鼠（5000 m，6 h d-1，6周），我们发现IHA低氧适应减少了梗死面积和乳酸脱氢酶和肌酸激酶-MB的血浆渗漏。此外，心肌中ZFP 580的表达被IHA缺氧上调。与此结果相一致，缺氧预处理组培养的H9 c2心肌细胞在模拟I/R损伤（3 h模拟缺血缺氧和2 h复氧）后，ZFP 580的表达明显高于对照组。为了确定ZFP 580在细胞凋亡中的作用，在模拟I/R暴露前72小时在H9 c2细胞中进行慢病毒介导的基因转染。结果表明，ZFP 580过表达可显著抑制I/R诱导的细胞凋亡和caspase-3的激活。用或不用ERK 1/2磷酸化抑制剂PD 98059预处理H9 c2细胞，Western blot结果显示PD 98059（10 µM）显著抑制I/R诱导的ZFP 580表达上调。我们的研究结果表明，IHA缺氧对I/R损伤的心脏保护作用是通过ZFP 580介导的，ZFP 580是ERK 1/2信号转导的下游靶点，在心肌细胞中具有抗凋亡作用。
ZFP580 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. After 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. Our 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.
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作者：
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通讯作者：
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作者：
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DOI：
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发表时间：
2010-05-07
影响因子：
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DOI：
10.1152/ajpheart.00100.2009
发表时间：
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