title: AMP-activated protein kinase-dependent autophagy mediated the protective effect of sonic hedgehog pathway on oxygen glucose deprivation-induced injury of cardiomyocytes.
abstract: 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.
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou 510182, PR China; Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, PR China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Guangzhou Research Institute of Snake Venom, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Guangzhou Research Institute of Snake Venom, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: He
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Kui-Xiang
authors.initials: KX
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Guangzhou First Municipal People's Hospital Affiliated to Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Jian-Wei
authors.initials: JW
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou 510182, PR China.
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Guangzhou Medical University, Guangzhou 510182, PR China; Guangzhou Institute of Cardiovascular Disease, Guangzhou Key Laboratory of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, PR China. Electronic address: jiandongluo@hotmail.com.
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Luo
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D002316:Cardiotonic Agents / Q000378:metabolism; D015687:Cell Hypoxia; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D005947:Glucose / Q000172:deficiency; D053823:Hedgehog Proteins / Q000378:metabolism*; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D015398:Signal Transduction
chemical_list: D002316:Cardiotonic Agents; D053823:Hedgehog Proteins; C546888:Shh protein, rat; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: Autophagy; Cardiomyocytes; Oxygen glucose deprivation; Sonic hedgehog pathway