High-glucose induces cardiac myocytes apoptosis through Foxo1/GRK2 signaling pathway
High-glucose induces cardiac myocytes apoptosis through Foxo1/GRK2 signaling pathway
复制标题
高糖通过Foxo1/GRK2信号通路诱导心肌细胞凋亡
DOI：
10.1016/j.bbrc.2019.03.193
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发表时间：
2019-05-21
影响因子：
3.1
通讯作者：
Wang, Yulin
中科院分区：
文献类型：
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作者：
Yang, Ming;Lin, Yanliang;Wang, Yulin
高糖诱导的心肌细胞凋亡已被证实，但其机制尚不清楚。在这项研究中，我们发现心脏H9c2细胞暴露于高糖促进Foxo1和GRK2的表达，并诱导自噬。进一步研究表明，高糖同时增加细胞质和细胞核Foxol的表达。Foxo1的抑制降低了GRK2的表达，阻断了自噬，增强了高糖诱导的细胞凋亡。GRK2基因敲低并不显著影响Foxo1的表达和自噬，但减弱了高糖诱导的细胞凋亡。有趣的是，GRK2敲低减少了ROS的产生。NAC处理不仅降低了细胞质和细胞核Foxo1的水平，而且抑制了GRK2的表达和自噬，显著减少了高糖诱导的细胞凋亡。抑制自噬对Foxo 1和GRK 2的表达无明显影响，但增加了高糖诱导的细胞凋亡。ChIP实验和荧光素酶报告基因实验证实Foxo1正调控GRK2的转录。这些结果表明Foxo1通过调节GRK2表达和自噬参与葡萄糖诱导的细胞凋亡。(C)2019爱思唯尔公司All rights reserved.
High glucose-induced cardiac myocytes apoptosis has been well demonstrated, but the mechanism remains unknown. In this study, we found that exposure of cardiac H9c2 cells to high glucose promoted Foxo1 and GRK2 expression, and induced autophagy. Further investigation showed that high glucose simultaneously increased the expression of cytoplasmic and nuclear Foxol. Inhibition of Foxo1 reduced GRK2 expression and blocked autophagy, enhancing high glucose-induced apoptosis. GRK2 knockdown did not significantly affect Foxo1 expression and autophagy, but attenuated high glucose-induced apoptosis. Intriguingly, GRK2 knockdown reduced ROS generation. NAC treatment not only reduced the levels of cytoplasmic and nuclear Foxo1, but also inhibited GRK2 expression and autophagy, remarkably reducing high glucose-induced apoptosis. Inhibition of autophagy did not notably affect the expression of Foxo1 and GRK2, but enlarged high glucose-induced apoptosis. ChIP assay and Luciferase reporter assay confirmed that Foxo1 positively regulated GRK2 transcription. These results suggested that Foxo1 was involved in glucose-induced apoptosis by regulating GRK2 expression and autophagy. (C) 2019 Elsevier Inc. All rights reserved.