Ca+2 Concentrations are Key Determinants of Ischemia-Reperfusion-Induced Apoptosis: Significance for the Molecular Mechanism of Bcl-2 Action
Ca+2 Concentrations are Key Determinants of Ischemia-Reperfusion-Induced Apoptosis: Significance for the Molecular Mechanism of Bcl-2 Action
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DOI：
10.1007/s12010-009-8761-2
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发表时间：
2010-04-01
影响因子：
3
通讯作者：
Wahi, Arun Kumar
中科院分区：
文献类型：
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作者：
Chattopadhyay, Pronobesh;Chaudhury, Pallab;Wahi, Arun Kumar
抗凋亡癌基因Bcl2和钙离子调控在缺血再灌注损伤中的作用机制尚不清楚。在本研究中，我们研究了线粒体Ca+2超载及Bcl2的作用机制。18只Wistar大鼠随机分为假手术对照组(I组)、缺血再灌注组(II组)和氨氯地平组(1 mg kg(-1)体重/d，连续7d)(III组)(n=6)。大鼠肝脏缺血1h，再灌流3h。测定线粒体Ca~(2+)含量，用透射电子显微镜观察线粒体损伤情况。线粒体Ca~(2+)水平的降低与细胞凋亡和细胞病变的减少有关。与假手术组相比，缺血再灌注组表现为钙离子超载，Bcl-2表达降低，次级内质网减少。因此，Bcl2依赖的钙离子减少是缺血再灌注损伤中抗细胞凋亡程序的重要组成部分。
The mechanism of action of the anti-apoptotic oncogene Bcl-2 and Ca+2 regulation in ischemia-reperfusion injury is still obscure. In this present study, we investigated mitochondrial Ca+2 overloads and mechanism of action of Bcl-2. Eighteen Wistar rats were divided into sham-operated control group (I) (n=6), ischemia and reperfusion group (II) (n=6), and amlodipine-treated group (1 mg kg(-1) body weight/daily by oral route for 7 days before inducing ischemia-reperfusion maneuver) (III) (n=6). Rats were subjected to 1 h of hepatic ischemia followed by 3-h reperfusion. Mitochondrial Ca2+ content was determined and damage was confirmed by transmission electron microscopy. Decrease of mitochondrial Ca+2 level is related to reduction of apoptosis and cellular changes, viz. increased Bcl-2 expression followed by reduction in secondary endoplasmic reticulum, whereas ischemia/reperfusion group shows overloading Ca+2 ions and decrease in Bcl-2 expression as compared to sham-operated rats. Thus, Bcl-2-dependent reduction of Ca+2 is an important component of the anti-apoptotic program in ischemia-reperfusion injury.