title: Nerve growth factor-induced Akt/mTOR activation protects the ischemic heart via restoring autophagic flux and attenuating ubiquitinated protein accumulation.
abstract: The dysregulation of autophagy is related to a variety of cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R). Nerve growth factor (NGF) has been shown to have therapeutic potential in ischaemic heart injury. In this study, we demonstrate that NGF administration can accelerate autophagic flux and attenuate protein ubiquitination in myocardial I/R heart. Our results showed that NGF could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury. The protective effect of NGF is associated with the inhibition of autophagy related proteins. On another hand, NGF enhances the clearance of ubiquitinated protein and increases the survival of myocardial cell in vivo and in vitro. Additionally, NGF could activate the PI3K/AKT and mTOR signaling pathways. These results suggested that the cardioprotective effect of NGF is related to the restoration of autophagic flux and attenuation of protein ubiquitination via the activation of PI3K/AKT and mTOR pathway.
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.|Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.|Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, 130012, China.
authors.forename: Zhou-Guang
authors.initials: ZG
authors.lastname: Wang
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Xiao-Fan
authors.initials: XF
authors.lastname: Wang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Yu
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Xue-Qiang
authors.initials: XQ
authors.lastname: Guang
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Hong-Yu
authors.initials: HY
authors.lastname: Zhang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Ying-Zheng
authors.initials: YZ
authors.lastname: Zhao
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.|Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, 130012, China.
authors.forename: Xiao-Kun
authors.initials: XK
authors.lastname: Li
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Rong-Zhou
authors.initials: RZ
authors.lastname: Wu
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Mao-Ping
authors.initials: MP
authors.lastname: Chu
authors.affiliation: Institute of Cardiovascular Development and Translational Medicine, Children's Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China.|Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xiao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology*; D020932:Nerve Growth Factor / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D057149:Ubiquitinated Proteins / Q000378:metabolism
chemical_list: D057149:Ubiquitinated Proteins; D020932:Nerve Growth Factor; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: NGF; PI3K/Akt/mTOR; autophagy; myocardial ischemia/reperfusion; ubiquitin