糖原合酶
蛋白激酶B
化学
葛兰素史克-3
内分泌学
内科学
信号转导
碳水化合物代谢
糖原
糖原磷酸化酶
细胞凋亡
细胞生物学
生物
生物化学
医学
作者
Xuehan Wu,Weiqi Huang,Minxue Quan,Yongqi Chen,Jiaxin Tu,Jie Zhou,Hong‐Bo Xin,Yisong Qian
标识
DOI:10.1139/bcb-2019-0247
摘要
Brain-type glycogen phosphorylase (pygb) is one of the rate-limiting enzymes in glycogenolysis that plays a crucial role in the pathogenesis of type 2 diabetes mellitus. Here we investigated the role of pygb in high-glucose (HG)-induced cardiomyocyte apoptosis and explored the underlying mechanisms, by using the specific pygb inhibitors or pygb siRNA. Our results show that inhibition of pygb significantly attenuates cell apoptosis and oxidative stress induced by HG in H9c2 cardiomyocytes. Inhibition of pygb improved glucose metabolism in cardiacmyocytes, as evidenced by increased glycogen content, glucose consumption, and glucose transport. Mechanistically, pygb inhibition activates the Akt–GSK-3β signaling pathway and suppresses the activation of NF-κB in H9c2 cells exposed to HG. Additionally, pygb inhibition promotes the expression and the translocation of hypoxia-inducible factor-1α (HIF-1α) after HG stimulation. However, the changes in glucose metabolism and HIF-1α activation mediated by pygb inhibition are significantly reversed in the presence of the Akt inhibitor MK2206. In conclusion, this study found that inhibition of pygb prevents HG-induced cardiomyocyte apoptosis via activation of Akt–HIF-α.
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