Brief exposure to carbon monoxide preconditions cardiomyogenic cells against apoptosis in ischemia-reperfusion
Brief exposure to carbon monoxide preconditions cardiomyogenic cells against apoptosis in ischemia-reperfusion
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DOI：
10.1016/j.bbrc.2010.02.017
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发表时间：
2010-03-12
影响因子：
3.1
通讯作者：
Yoshida, Ken-ichi
中科院分区：
文献类型：
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作者：
Kondo-Nakamura, Mihoko;Shintani-Ishida, Kaori;Yoshida, Ken-ichi
我们研究了一氧化碳预处理是否以及如何阻止心肌细胞缺血再灌注时H9c2细胞的凋亡。短暂缺血（10分钟）后再灌注（6小时）诱导细胞色素c释放、caspase-9和caspase-3的激活和凋亡核凝聚。短暂的CO预处理（10分钟）或caspase-9抑制剂（Z-LEHD-FMK）可减弱这些凋亡变化。缺血-再灌注增加Akt在Ser472/473/474位点的磷酸化，CO预处理增强了这一作用。一种特异性Akt抑制剂（API-2）减弱了CO在再灌注中的抗凋亡作用。在常氧细胞中，CO增强了O-2（-）的生成，线粒体复合物III抑制剂（抗霉素a）抑制了O-2（-）的生成，但NADH氧化酶抑制剂（apocynin）不抑制O-2的生成。co增强的Akt磷酸化被O-2（-）清除剂（铁）、过氧化氢酶或超氧化物歧化酶（SOD）抑制剂（DETC）抑制。这些结果表明，CO预处理诱导线粒体生成O-2(-)，然后由SOD转化为H2O2， H2O2随后激活Akt，从而减弱缺血-再灌注时的凋亡。(C) 2010爱思唯尔公司版权所有。
We examined whether and how pretreatment with carbon monoxide (CO) prevents apoptosis of cardioblastic H9c2 cells in ischemia-reperfusion. Reperfusion (6 h) following brief ischemia (10 min) induced cytochrome c release, activation of caspase-9 and caspase-3, and apoptotic nuclear condensation. Brief CO pretreatment (10 min) or a caspase-9 inhibitor (Z-LEHD-FMK) attenuated these apoptotic changes. Ischemia-reperfusion increased phosphorylation of Akt at Ser472/473/474, and this was enhanced by CO pretreatment. A specific Akt inhibitor (API-2) blunted the anti-apoptotic effects of CO in reperfusion. In normoxic cells, CO enhanced O-2(-) generation, which was inhibited by a mitochondrial complex III inhibitor (antimycin A) but not by a NADH oxidase inhibitor (apocynin). The CO-enhanced Akt phosphorylation was suppressed by an O-2(-) scavenger (Tiron), catalase or a superoxide dismutase (SOD) inhibitor (DETC). These results suggest that CO pretreatment induces mitochondrial generation of O-2(-), which is then converted by SOD to H2O2, and subsequent Akt activation by H2O2 attenuates apoptosis in ischemia-reperfusion. (C) 2010 Elsevier Inc. All rights reserved.