Regulation of Na+‐K+‐ATPase effected high glucose‐induced myocardial cell injury through c‐Src dependent NADPH oxidase/ROS pathway
Regulation of Na+‐K+‐ATPase effected high glucose‐induced myocardial cell injury through c‐Src dependent NADPH oxidase/ROS pathway
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DOI：
10.1016/j.yexcr.2017.05.023
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发表时间：
2017-08
影响因子：
3.7
通讯作者：
Xiaofei Yan;Meng Xun;Xiaojuan Dou;Litao Wu;Yan Han;Jin Zheng
中科院分区：
文献类型：
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作者：
Xiaofei Yan;Meng Xun;Xiaojuan Dou;Litao Wu;Yan Han;Jin Zheng
长期以来，据报道 Na+/K+-ATP 酶活性降低与糖尿病相关的心肌细胞死亡和心功能障碍有关。然而，在糖尿病相关心肌疾病中直接调节Na+-K+-ATP酶的性质仍不清楚。高血糖被认为是导致糖尿病相关心肌细胞凋亡和功能障碍的主要因素之一。本研究探讨哇巴因抑制Na+-K+-ATP酶或DRm217激活Na+-K+-ATP酶是否对高糖（HG）诱导的心肌损伤有作用。在这里，我们发现向 HG 处理的细胞中添加 DRm217 或哇巴因会产生相反的效果。 DRm217 减少，但哇巴因增加 HG 诱导的细胞损伤和凋亡。这是通过改变 Na+-K+-ATP 酶活性和 Na+-K+-ATP 酶细胞表面表达来介导的。 Na+-K+-ATP酶内吞作用的抑制减轻了HG诱导的ROS积累。 Na+-K+-ATPase·c-Src 依赖性 NADPH 氧化酶/ROS 途径也参与哇巴因和 DRm217 对 HG 诱导的细胞损伤的影响。这些新的结果可能有助于我们了解Na+-K+-ATP酶在糖尿病心血管疾病中的重要作用。
Depressed Na+/K+-ATPase activity has long been reported to be involved in diabetic-related cardiomyocyte death and cardiac dysfunction. However, the nature of directly regulating Na+-K+-ATPase in diabetic-related myocardial diseases remains unknown. Hyperglycemia is believed as one of major factors responsible for diabetic-related myocardial apoptosis and dysfunction. In this study, whether inhibiting Na+-K+-ATPase by ouabain or activating Na+-K+-ATPase by DRm217 has functions on high glucose (HG) -induced myocardial injury was investigated. Here we found that addition of DRm217 or ouabain to HG-treated cells had opposite effects. DRm217 decreased but ouabain increased HG-induced cell injury and apoptosis. This was mediated by changing Na+-K+-ATPase activity and Na+-K+-ATPase cell surface expression. The inhibition of Na+-K+-ATPase endocytosis alleviated HG-induced ROS accumulation. Na+-K+-ATPase·c-Src dependent NADPH oxidase/ROS pathway was also involved in the effects of ouabain and DRm217 on HG-induced cell injury. These novel results may help us to understand the important role of the Na+-K+-ATPase in diabetic cardiovascular diseases.