Nitric oxide during ischemia attenuates oxidant stress and cell death during ischemia and reperfusion in cardiomyocytes
Nitric oxide during ischemia attenuates oxidant stress and cell death during ischemia and reperfusion in cardiomyocytes
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DOI：
10.1016/j.freeradbiomed.2007.05.017
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发表时间：
2007-08-15
影响因子：
7.4
通讯作者：
Schumacker, Paul T.
中科院分区：
文献类型：
--
作者：
Iwase, Hirotaro;Robin, Emmanuel;Schumacker, Paul T.
一氧化氮（NO）被认为是缺血/再灌注（I/R）期间的心脏保护剂，但保护机制尚不清楚。氧化应激会导致 I/R 中的细胞死亡，因此我们测试了 NO 是否可以通过减弱氧化应激来发挥保护作用。在模拟缺血期间向心肌细胞和小鼠胚胎成纤维细胞施用NO（10-1200 nM），并在没有NO的再灌注期间评估细胞死亡。在每种情况下，NO 都消除了再灌注期间的细胞死亡。过度表达内皮一氧化氮合酶 (NOS) 的细胞表现出类似的保护作用，但这种保护作用被 NOS 抑制剂 N-omega-硝基-L-精氨酸甲酯所消除。保护作用不是由鸟苷酸环化酶或线粒体 K-ATP 通道介导的，因为这些系统的抑制剂无法消除保护作用。 NO 并不能阻止线粒体电位的降低，但用 NO 保护的细胞在再灌注时表现出电位的恢复。使用 C11-BODIPY 进行的测量表明，NO 可以减弱缺血和再灌注期间的脂质过氧化作用。使用比率氧化还原传感器 HSP-FRET 测量氧化应激表明，NO 会减弱缺血期间的蛋白质氧化。这些发现表明，缺血期间NO的生理水平可以减轻缺血期间和再灌注期间的氧化应激。这种反应与细胞死亡的显着减弱相关，表明缺血性细胞死亡可能是一种受调控的事件。 (c) 2007 Elsevier Inc. 保留所有权利。
Nitric oxide (NO) has been implicated as a cardioprotective agent during ischemia/reperfusion (I/R), but the mechanism of protection is unknown. Oxidant stress contributes to cell death in I/R, so we tested whether NO protects by attenuating oxidant stress. Cardiomyocytes and murine embryonic fibroblasts were administered NO (10-1200 nM) during simulated ischemia, and cell death was assessed during reperfusion without NO. In each case, NO abrogated cell death during reperfusion. Cells overexpressing endothelial NO synthase (NOS) exhibited a similar protection, which was abolished by the NOS inhibitor N-omega-nitro-L-arginine methyl ester. Protection was not mediated by guanylate cyclase or the mitochondrial K-ATP channel, as inhibitors of these systems failed to abolish protection. NO did not prevent decreases in mitochondrial potential, but cells protected with NO demonstrated recovery of potential at reperfusion. Measurements using C11-BODIPY reveal that NO attenuates lipid peroxidation during ischemia and reperfusion. Measurements of oxidant stress using the ratiometric redox sensor HSP-FRET demonstrate that NO attenuates protein oxidation during ischemia. These findings reveal that physiological levels of NO during ischemia can attenuate oxidant stress both during ischemia and during reperfusion. This response is associated with a remarkable attenuation of cell death, suggesting that ischemic cell death may be a regulated event. (c) 2007 Elsevier Inc. All rights reserved.