Nerve growth factor-induced Akt/mTOR activation protects the ischemic heart via restoring autophagic flux and attenuating ubiquitinated protein accumulation
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Zhou-Guang Wang1,2,3,*, Hao Li1,*, Yan Huang2,*, Rui Li2, Xiao-Fan Wang2, Li-Xia Yu2, Xue-Qiang Guang1, Lei Li1, Hong-Yu Zhang2, Ying-Zheng Zhao2, Chunxiang Zhang1, Xiao-Kun Li2,3, Rong-Zhou Wu1, Mao-Ping Chu1, Jian Xiao1,2
1Institute of Cardiovascular Development and Translational Medicine, Children’s Heart Center, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou 325027, China
2Molecular Pharmacology Research Center, School of Pharmacy, Key Laboratory of Biotechnology and Pharmaceutical Engineering, Wenzhou Medical University, Wenzhou 325035, China
3Department of Biochemistry and Molecular Biology, College of Basic Medical Science, Jilin University, Changchun, 130012, China
*These authors have contributed equally to this work
Jian Xiao, email: [email protected]
Mao-Ping Chu, email: [email protected]
Rong-Zhou Wu, email: [email protected]
Keywords: NGF, myocardial ischemia/reperfusion, autophagy, PI3K/Akt/mTOR, ubiquitin
Received: April 14, 2016 Accepted: December 06, 2016 Published: December 27, 2016
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.
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