AMP-activated protein kinase-dependent autophagy mediated the protective effect of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of cardiomyocytes.

AMP-activated protein kinase-dependent autophagy mediated the protective effect of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of cardiomyocytes.
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AMP 激活的蛋白激酶依赖性自噬介导声波刺猬通路对氧糖剥夺诱导的心肌细胞损伤的保护作用。

DOI:
10.1016/j.bbrc.2015.01.006
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发表时间:
2015-02
期刊:
Biochem Biophys Res Commun
影响因子:
--
通讯作者:
Luo JD
Luo JD
中科院分区:
其他
文献类型:
--
作者:
Chen KX;Zhu JW;Zhang GP;Luo JD

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已有研究表明Shh信号通路对心肌梗死后的心肌细胞具有保护作用,但其机制尚不清楚。在这里,我们提供的证据表明,Shh通路诱导心肌细胞存活通过AMP激活的蛋白激酶依赖性自噬。Shh信号通路激动剂SAG可诱导缺氧缺糖(OGD)1 h和4 h H9 c2心肌细胞LC 3-II表达增加,并诱导自噬体形成。此外,SAG诱导了一个深刻的AMP激活蛋白激酶(AMPK)的激活,然后直接磷酸化和激活下游的自噬启动Ulk 1,独立于自噬抑制哺乳动物雷帕霉素靶蛋白(mTOR)复合物1。总之,我们的研究结果表明,Shh激活OGD下心肌细胞中AMPK依赖性自噬,表明自噬在Shh诱导的细胞保护中发挥作用。
Sonic hedgehog (Shh) pathway has been reported to protect cardiomyocytes in myocardial infarction (MI), but the underlying mechanism is not clear. Here, we provide evidence that Shh pathway induces cardiomyocytes survival through AMP-activated protein kinase-dependent autophagy. Shh pathway agonist SAG increased the expression of LC3-II, and induced the formation of autophagosomes in cultured H9c2 cardiomyocytes under oxygen glucose deprivation (OGD) 1 h and 4 h. Moreover, SAG induced a profound AMP-activated protein kinase (AMPK) activation, and then directly phosphorylated and activated the downstream autophagy initiator Ulk1, independent of the autophagy suppressor mammalian target of rapamycin (mTOR) complex 1. Taken together, our results have shown that Shh activates AMPK-dependent autophagy in cardiomyocytes under OGD, suggesting a role of autophagy in Shh-induced cellular protection.
AMP激活的蛋白激酶对ULK1(HATG1)的磷酸化将能量传感连接到线粒体。
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