Insulin protects apoptotic cardiomyocytes from hypoxia/reoxygenation injury through the sphingosine kinase/sphingosine 1-phosphate axis.
Insulin protects apoptotic cardiomyocytes from hypoxia/reoxygenation injury through the sphingosine kinase/sphingosine 1-phosphate axis.
复制标题
胰岛素通过鞘氨醇激酶/1-磷酸鞘氨醇轴保护凋亡心肌细胞免受缺氧/复氧损伤
DOI：
10.1371/journal.pone.0080644
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Yu H;Che X;Xu X;Zheng M;Zhao Y;He W;Yu J;Xiong J;Li W
目的实验和临床研究表明，再灌注期间给予胰岛素具有心脏保护作用，但其机制尚不清楚。在这项研究中，胰岛素的能力，以保护凋亡心肌细胞缺氧/复氧损伤使用鞘氨醇激酶/鞘氨醇1-磷酸轴进行了研究。方法和结果分离大鼠心肌细胞并进行缺氧和复氧。用[γ-32 P] ATP测定鞘氨醇激酶活性。发现胰岛素增加鞘氨醇激酶活性。免疫细胞化学和Western印迹分析显示，鞘氨醇激酶1的亚细胞位置的变化，从细胞质的膜在心肌细胞。胰岛素可使心肌细胞内S1 P浓度增加，并呈剂量依赖性。FRET效率表明，胰岛素也反式激活S1 P1受体。TUNEL染色显示，复氧时给予胰岛素可降低复氧诱导的细胞凋亡率，这是SphK 1活性所必需的。它还降低了S1 P受体的活化速率，并抑制心肌细胞中缺氧/再氧合诱导的细胞死亡。结论鞘氨醇激酶1/鞘氨醇1-磷酸/S1 P受体轴是胰岛素保护缺氧/复氧损伤大鼠心肌细胞凋亡的途径之一。
Objective Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the mechanisms underlying this effect are still unknown. In this study, the ability of insulin to protect apoptotic cardiomyocytes from hypoxia/reoxygenation injury using the sphingosine kinase/sphingosine 1-phosphate axis was investigated. Methods and Results Rat cardiomyocytes were isolated and subjected to hypoxia and reoxygenation. [γ-32P] ATP was used to assess sphingosine kinase activity. Insulin was found to increase sphingosine kinase activity. Immunocytochemistry and Western blot analysis showed changes in the subcellular location of sphingosine kinase 1 from cytosol to the membrane in cardiomyocytes. Insulin caused cardiomyocytes to accumulate of S1P in a dose-dependent manner. FRET efficiency showed that insulin also transactivates the S1P1 receptor. TUNEL staining showed that administration of insulin during reoxygenation could to reduce the rate of reoxygenation-induced apoptosis, which is a requirement for SphK 1 activity. It also reduced the rate of activation of the S1P receptor and inhibited hypoxia/reoxygenation-induced cell death in cardiomyocytes. Conclusion The sphingosine kinase 1/sphingosine 1-phosphate/S1P receptor axis is one pathway through which insulin protects rat cardiomyocytes from apoptosis induced by hypoxia/reoxygenation injury.
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