Prohibitin protects against oxidative stress-induced cell injury in cultured neonatal cardiomyocyte
Prohibitin protects against oxidative stress-induced cell injury in cultured neonatal cardiomyocyte
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DOI：
10.1007/s12192-008-0086-5
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发表时间：
2009-05-01
影响因子：
3.8
通讯作者：
Qian, LingJia
中科院分区：
文献类型：
--
作者：
Liu, XiaoHua;Ren, Zhe;Qian, LingJia
氧化应激是心肌损伤的主要原因之一，与心肌细胞死亡有关。线粒体在氧化应激下触发心肌细胞的坏死和凋亡途径中起着关键作用。尽管禁止素(PHB)被认为是一种线粒体伴侣，但其在心肌细胞中的功能尚不清楚。本研究旨在探讨PHB对心肌线粒体的保护作用。氧化应激可使线粒体PHB含量增加，且呈时间依赖性。携带PHB正义基因的重组腺病毒载体在培养的心肌细胞中过表达PHB，导致线粒体PHB含量增加。与未转染的心肌细胞相比，PHB过表达可保护线粒体免受氧化应激损伤。在PHB过表达的心肌细胞中，过氧化氢(H_2O_2)处理后，线粒体介导的凋亡途径一直受到抑制，包括线粒体膜通透性转换的改变减少，细胞色素c从线粒体释放到细胞质受到抑制。结果，氧化应激诱导的心肌细胞凋亡受到抑制。提示PHB对氧化应激诱导的心肌细胞损伤具有保护作用，增加线粒体PHB含量是心肌损伤治疗的新靶点。
Oxidative stress is one of the main causes of myocardial injury, which is associated with cardiomyocyte death. Mitochondria play a key role in triggering the necrosis and apoptosis pathway of cardiomyocytes under oxidative stress. Although prohibitin (PHB) has been acknowledged as a mitochondrial chaperone, its functions in cardiomyocytes are poorly characterized. The present research was designed to investigate the cardioprotective role of PHB in mitochondria. Oxidative stress can increase the PHB content in mitochondria in a time-dependent manner. Overexpression of PHB in cultured cardiomyocytes by transfection of recombinant adenovirus vector containing PHB sense cDNA resulted in an increase of PHB in mitochondria. Compared with the non-transfection cardiomyocytes, PHB overexpression could protect the mitochondria from oxidative stress-induced injury. The mitochondria-mediated apoptosis pathway was consistently suppressed in PHB-overexpressed cardiomyocytes after hydrogen peroxide (H2O2) treatment, including a reduced change in mitochondrial membrane permeability transition and an inhibited release of cytochrome c from mitochondria to cytoplasma. As a result, the oxidative stress-induced cardiomyocyte apoptosis was suppressed. These data indicated that PHB protected the cardiomyocytes from oxidative stress-induced damage, and that increasing PHB content in mitochondria constituted a new therapeutic target for myocardium injury.