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NEDD4-1 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis via the PI3K/Akt pathway

Activation of the Akt pathway has been shown to protect the heart from ischaemia/reperfusion (I/R) injury. NEDD4-1 has been shown to positively regulate nuclear trafficking of the activated form of Akt. However, the role of NEDD4-1 in cardiac I/R injury remains to be elucidated. In the present study...

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Published in:Apoptosis (London) 2017-03, Vol.22 (3), p.437-448
Main Authors: Hu, Wei, Zhang, Peng, Gu, Jun, Yu, Qiang, Zhang, Dadong
Format: Article
Language:English
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Summary:Activation of the Akt pathway has been shown to protect the heart from ischaemia/reperfusion (I/R) injury. NEDD4-1 has been shown to positively regulate nuclear trafficking of the activated form of Akt. However, the role of NEDD4-1 in cardiac I/R injury remains to be elucidated. In the present study, Lentiviral vectors were constructed to overexpress or knockdown NEDD4-1 in H9c2 cardiomyocytes subjected to I/R injury or ischemic preconditioning (IPC). The results indicated that NEDD4-1 levels were decreased after I/R and increased after IPC in rat heart tissue and in H9c2 cardiomyocytes. Overexpression of NEDD4-1 activated the Akt pathway and regulated apoptosis-related proteins in H9c2 cardiomyocytes, attenuating SI/R-induced cell apoptosis and caspase 3/7 activities. Furthermore, in vivo overexpression of NEDD4-1 attenuated myocardial apoptosis following myocardial I/R. Our results demonstrated that NEDD4-1 protects the myocardium from I/R induced apoptosis by activating PI3K/Akt signaling.
ISSN:1360-8185
1573-675X
DOI:10.1007/s10495-016-1326-2