Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia-reperfusion
Increased expression of calcium-sensing receptors induced by ox-LDL amplifies apoptosis of cardiomyocytes during simulated ischaemia-reperfusion
复制标题
ox-LDL诱导的钙敏感受体表达增加会放大模拟缺血再灌注期间心肌细胞的凋亡
DOI：
10.1111/j.1440-1681.2010.05345.x
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发表时间：
2010-03-01
影响因子：
2.9
通讯作者：
Xu, Chang-Qing
中科院分区：
文献类型：
--
作者：
Guo, Jin;Li, Hong-Zhu;Xu, Chang-Qing
P>1。急性心肌梗死（AMI）与动脉粥样硬化密切相关，是世界范围内发病率和死亡率最高的疾病。动脉粥样硬化和AMI的发病机制目前还不清楚。钙敏感受体（CaSR）是G蛋白偶联受体超家族的成员。已有研究表明，在大鼠动脉粥样硬化的心脏组织中，CaSR的表达增加。CaSR在心肌缺血再灌注损伤、细胞凋亡和心肌肥大中起重要作用。然而，CaSR表达的增加是否影响心肌细胞对AMI的敏感性仍有待确定。本研究采用培养的新生大鼠心室心肌细胞，研究氧化低密度脂蛋白（ox-LDL）、缺血再灌注、GdCl 3（CaSR激动剂）和NPS-2390（CaSR拮抗剂）对CaSR表达的影响。分析细胞凋亡数量、细胞形态学改变、细胞内钙离子浓度（[Ca 2 +]（i））和关键线粒体途径的组成. ox-LDL处理的心肌细胞CaSR、细胞色素c（cyt-c）、Bax和活化的caspase 3（17 kD）表达上调，Bcl-2表达下调，[Ca ~（2+）]（i）升高，细胞凋亡。GdCl 3的应用增强了这种作用，而GdCl-2390则降低了CaSR的表达，减轻了凋亡.总之，发现ox-LDL以依赖于时间和剂量的方式增加CaSR的表达。在模拟缺血-再灌注过程中，它也增加了新生大鼠培养的心室肌细胞的凋亡。
P>1. Acute myocardial infarction (AMI) is strongly associated with atherosclerosis, and is responsible for significant morbidity and mortality worldwide. The pathogenic mechanisms that underlie atherosclerosis and AMI are undefined at present. The calcium-sensing receptor (CaSR) is a member of the superfamily of G-protein coupled receptors. It has been demonstrated previously that the expression of CaSR is increased in atherosclerotic cardiac tissue of rats. It has also been suggested that CaSR has a crucial role in cardiac ischaemia-reperfusion injury, apoptosis and hypertrophy. However, it remains to be determined whether an increase in the expression of CaSR influences the sensitivity of cardiomyocytes to AMI.2. The present study used cultured ventricular cardiomyocytes from neonatal rats to investigate the effect of oxidized low-density lipoprotein (ox-LDL), ischaemia-reperfusion, GdCl3 (an agonist of CaSR) and NPS-2390 (an antagonist of CaSR) on the expression of CaSR. The amount of apoptosis, alterations in the morphology of the cells, the intracellular calcium concentration ([Ca2+](i)) and components of critical mitochondrial pathways were also analysed.3. Cardiomyocytes treated with ox-LDL showed upregulated expression of CaSR, cytochrome c (cyt-c), Bax and activated caspase 3 (17 kD) and downregulated expression of Bcl-2, as well as elevated [Ca2+](i) and apoptosis. Application of GdCl3 augmented these effects, and NPS-2390 decreased the expression of CaSR and reduced apoptosis.4. In conclusion, ox-LDL was found to increase the expression of CaSR in a manner that was dependent on time and dose. It also augmented apoptosis during simulated ischaemia-reperfusion in cultured ventricular cardiomyocytes from neonatal rats.