Role of opioid delta1 receptors, mitochondrial K(ATP) channels, and protein kinase C during cardiocyte apoptosis.
Role of opioid delta1 receptors, mitochondrial K(ATP) channels, and protein kinase C during cardiocyte apoptosis.
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DOI：
10.1006/jmcc.2001.1464
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发表时间：
2001-11
影响因子：
5
通讯作者：
Huiping Liu;Hong Yan Zhang;B. C. McPherson;T. Baman;S. Roth;Z. Shao;Xiangdong Zhu;Z. Yao
中科院分区：
文献类型：
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作者：
Huiping Liu;Hong Yan Zhang;B. C. McPherson;T. Baman;S. Roth;Z. Shao;Xiangdong Zhu;Z. Yao
阿片类药物可减轻缺血再灌流后的心脏损伤。我们想确定阿片类药物的保护作用是否是通过阻止心肌细胞凋亡来介导的，如果是的话，我们想要描述阿片类Delta1受体和蛋白激酶C(PKC)在这一作用中的作用。鸡胚心肌细胞在模拟缺血12h后复氧12h，流式细胞仪检测细胞凋亡率为54+/-3%(n=6)。这一结果与DNA梯状条带和TUNEL法结果一致。预适应可减少细胞凋亡率(36+/-4%，n=6)。预先给予选择性阿片受体阻断剂苯妥英钠(0.1micromol/L)可阻断预适应的作用(57+/-5%，n=6)。选择性阿片受体激动剂BW373U86(20pmol/L)也可抑制细胞凋亡(39+/-3%，n=6*v对照)。这些作用可被选择性线粒体K通道阻断剂(50+/-5%，n=6)和特异性蛋白激酶C抑制剂GO-6976(0.1微克/L)所阻断。预适应和BW373U86均可在模拟缺血前激活颗粒组分的PKC Delta亚型，但对总组分和胞浆组分无影响。刺激阿片类Delta1受体激活培养的心室肌细胞线粒体K(ATP)通道和PKC Delta亚型。这是缺血预适应阻断细胞凋亡、保护心功能的重要信号转导途径之一。
Opioids attenuate cardiac injury after ischemia and reperfusion. We wanted to determine whether the protection of opioids is mediated by blocking cardiocyte apoptosis, and if so, to describe the role of opioid delta1 receptors and protein kinase C (PKC) in this effect. Chick embryonic cardiomyocytes were subjected to 12 h of simulated ischemia and then 12 h of re-oxygenation, which resulted in 54+/-3% (n=6) of cell apoptosis (n=6) as measured by flow cytometry. This result was consistent with DNA laddering and TUNEL assay. Preconditioning, elicited with three cycles of 1 min of simulated ischemia separated by 5 min of reoxygenation before prolonged simulated ischemia, reduced apoptosis (36+/-4%, n=6*). Pretreatment with BNTX (0.1 micromol/l), a selective opioid delta1 receptor blocker, abolished the effects of preconditioning (57+/-5%, n=6). The selective opioid delta receptor agonist BW373U86 (20 pmol/l) also attenuated apoptosis (39+/-3%, n=6* v control). These effects were abolished by 5-hydroxydecanoate (100 microm), a selective mitochondrial K(ATP) channel blocker (50+/-5%, n=6) and by Go-6976 (0.1 micromol/l), a specific PKC inhibitor. Both preconditioning and BW373U86 activated the PKC delta isoform of particulate fraction before simulated ischemia without effect on total and cytosolic fractions. Stimulation of opioid delta1 receptors activates mitochondrial K(ATP) channels and the PKC delta isoform in cultured ventricular myocytes. This is one important signal transduction pathway through which ischemic preconditioning blocks apoptosis and preserves cardiac function.