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

• Published in: Biochemical and biophysical research communications Vol. 457; no. 3; pp. 419 - 425
• Main Authors: Xiao, Qing, Yang, Ya, Qin, Yuan, He, Yan-Hua, Chen, Kui-Xiang, Zhu, Jian-Wei, Zhang, Gui-Ping, Luo, Jian-Dong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.02.2015
• Subjects: AMP-Activated Protein Kinases - metabolism; Animals; Autophagy; Autophagy - physiology; Cardiomyocytes; Cardiotonic Agents - metabolism; Cell Hypoxia; Cell Line; Cell Survival - physiology; Glucose - deficiency; Hedgehog Proteins - metabolism; Myocardial Infarction - metabolism; Myocardial Infarction - pathology; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; Oxygen glucose deprivation; Rats; Signal Transduction; Sonic hedgehog pathway; Cardiomyocytes; Oxygen glucose deprivation; Autophagy; Sonic hedgehog pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.01.006

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. •Shh pathway induced autophagy in CMs under OGD.•Autophagy inhibition impaired the protective role of Shh pathway in CMs.•Shh pathway induced autophagy through direct AMPK and ULK1 binding.