Inhibition of cytochrome c release by 10-N-nonyl acridine orange, a cardiolipin-specific dye, during myocardial ischemia-reperfusion in the rat.
Inhibition of cytochrome c release by 10-N-nonyl acridine orange, a cardiolipin-specific dye, during myocardial ischemia-reperfusion in the rat.
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DOI：
10.1152/ajpheart.00938.2009
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发表时间：
2010-02
期刊：
影响因子：
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通讯作者：
Guo-Xing Zhang;S. Kimura;K. Murao;K. Obata;H. Matsuyoshi;M. Takaki
中科院分区：
文献类型：
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作者：
Guo-Xing Zhang;S. Kimura;K. Murao;K. Obata;H. Matsuyoshi;M. Takaki
细胞色素c从线粒体释放到胞浆是缺血再灌注（I/R）诱导的心肌组织损伤中下游caspase介导的凋亡信号转导的关键步骤。10-N-壬基吖啶橙子（NAO），一种心磷脂特异性染料，已被证明可以抑制离体线粒体中Bid介导的细胞色素c释放;然而，NAO可能的保护作用和保护大鼠模型中心肌I/R诱导的组织损伤的机制尚不清楚。雄性Sprague-Dawley大鼠进行30分钟的冠状动脉闭塞，然后再灌注。所有大鼠在闭塞前10分钟接受媒介物或NAO（100 μ g/kg iv）。与溶剂处理的大鼠相比，再灌注后24小时，NAO处理的大鼠心脏梗死面积显着减少。NAO处理显著降低缺血区细胞色素c含量和caspase-9活性，但不影响caspase-8活性。此外，NAO治疗显着抑制易位截短出价，促凋亡Bcl-2家族成员，线粒体部分。NAO还抑制钙超载引起的线粒体肿胀和氧摄取。结果提示，NAO对心肌I/R损伤具有保护作用，其机制可能是通过阻断截断型Bid向线粒体的转运，抑制线粒体通透性转换孔的开放，从而抑制细胞色素c的释放。
The release of cytochrome c from the mitochondria to the cytosol is a critical step for downstream caspase-mediated apoptotic signal transduction in ischemia-reperfusion (I/R)-induced myocardial tissue injury. 10-N-nonyl acridine orange (NAO), a cardiolipin-specific dye, has been shown to inhibit Bid-mediated cytochrome c release from isolated mitochondria in vitro; however, the possible protective effects of NAO and the mechanisms underlying the protection from myocardial I/R-induced tissue injury in a rat model are unknown. Male Sprague-Dawley rats were subjected to a 30-min coronary arterial occlusion followed by reperfusion. All rats received either vehicle or NAO (100 microg/kg iv) 10 min before the occlusion. The infarct size in the heart at 24 h after reperfusion was significantly reduced in NAO-treated rats compared with vehicle-treated rats. NAO treatment significantly reduced the cytosolic cytochrome c contents and caspase-9 activity in the ischemic region but did not affect caspase-8 activity. Furthermore, NAO treatment markedly suppressed the translocation of truncated Bid, a proapoptotic Bcl-2 family member, to the mitochondrial fraction. NAO also suppressed the mitochondrial swelling and oxygen uptake stimulated by calcium overload. The results suggest that NAO possesses protective effects against myocardial I/R injury, which may be due to the suppression of cytochrome c release through blockade of truncated Bid translocation to mitochondria and inhibition of the opening of mitochondrial permeability transition pores.