Overexpression of PHGPx and HSP60/10 protects against ischemia/reoxygenation injury
Overexpression of PHGPx and HSP60/10 protects against ischemia/reoxygenation injury
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DOI：
10.1016/s0891-5849(03)00400-3
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发表时间：
2003-10-01
影响因子：
7.4
通讯作者：
Dillmann, WH
中科院分区：
文献类型：
--
作者：
Hollander, JM;Lin, KM;Dillmann, WH
缺血/再灌注（I/R）引起的活性氧对心脏组织造成损伤。我们研究了线粒体磷脂氢过氧化物谷胱甘肽过氧化物酶（mPHGPx）和胞浆PHGPx（cPHGPx）过表达对保护新生大鼠心肌细胞（NCM）免受模拟I/R的影响。此外，研究了热休克蛋白60和10（HSP 60/10）的保护性组合效应。用表达mPHGPx、cPHGPx、HSP 60/10的腺病毒载体或空对照（Adv-）感染NCM，并进行8小时的缺血，随后16小时的复氧。mPHGPx感染导致I/R后丙二醛和4-羟基-2（E）-壬烯醛减少40%（p <0.05）。肌酸激酶和乳酸脱氢酶释放在mPHGPx感染和HSP 60/10感染的细胞中均降低（p <0.05）。mPHGPx和HSP 60/10过表达的组合导致进一步的保护（p <0.01）。在PHGPx和HSP 60/10感染的细胞中，DNA梯状和组蛋白相关的DNA片段减少（p <0.01）。在mPHGPx感染的细胞中，线粒体释放的细胞色素c减少。此外，mPHGPx过表达在模拟I/R后保留了电子传递链复合物IV功能（p <0.05）。这些结果表明，PHGPx的过表达提供了对由模拟I/R损伤引起的损伤的保护，特别是在线粒体中，并且mPHGPx和HSP 60/10的组合赋予了额外的保护作用。(C)2003年爱思唯尔公司
Reactive oxygen species arising from ischemia/reperfusion (I/R) cause damage to cardiac tissue. We examined the effects of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mPHGPx) and cytosolic PHGPx (cPHGPx) overexpression on protection against simulated I/R in neonatal rat cardiac myocytes (NCM). Additionally, a protective combinatorial effect with heat shock proteins 60 and 10 (HSP60/10) was investigated. NCM were infected with adenoviral vectors expressing mPHGPx, cPHGPx, HSP60/10, or an empty control (Adv-) and submitted to 8 h of ischemia followed by 16 h of reoxygenation. mPHGPx infection led to a 40% decrease in malondialdehyde and 4-hydroxy-2(E)-nonenal following I/R (p < .05). Creatine kinase and lactate dehydrogenase release were decreased in both mPHGPx-infected and HSP60/10-infected cells (p < .05). The combination of mPHGPx and HSP60/10 overexpression led to further protection (p < .01). DNA laddering and histone-associated DNA fragments were decreased in PHGPx- and HSP60/10-infected cells (p < .01). Cytochrome c release from mitochondria was decreased in mPHGPx-infected cells. Furthermore, mPHGPx overexpression preserved electron transport chain complex IV function following simulated I/R (p < .05). These results indicate that overexpression of PHGPx provides protection against damage resulting from simulated I/R injury, particularly in the mitochondria, and that the combination of mPHGPx and HSP60/10 imparts an added protective effect. (C) 2003 Elsevier Inc.