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

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Abstract

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.

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Abbreviations

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

IGF:

Insulin-like growth factor

IPC:

Ischemic preconditioning

I/R:

Ischaemia/reperfusion

LCA:

Left coronary artery

LDH:

Lactate dehydrogenase

NEDD4-1:

Neural precursor cell expressed developmentally down-regulated 4-1

PI:

Propidium iodide

PI3K:

Phosphatidylinositol 3-kinase

PTEN:

Phosphatase and tensin homolog

TUNEL:

Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling

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Acknowledgements

W.H. designed the study, participated in data analysis, and wrote the article. P.Z. performed the experiments, participated in data analysis, and wrote the article. J.G., Q.Y., and D.Z. performed the experiments, data acquisition. This study was supported by the Shanghai Medical Key Specialty Construction Projects (Class A, No. ZK2012A24 and ZK2015A10), the Key Project from the Shanghai Municipal Commission of Health and Family Planning (No. 201640029), and the Min Hang District Science and Technology Committee (No. 2016MHZ70).

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Authors and Affiliations

  1. Department of Cardiology, Minhang Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, 201199, China

    Wei Hu, Peng Zhang, Jun Gu, Qiang Yu & Dadong Zhang

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  1. Wei Hu
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Correspondence to Wei Hu.

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Hu, W., Zhang, P., Gu, J. et al. NEDD4-1 protects against ischaemia/reperfusion-induced cardiomyocyte apoptosis via the PI3K/Akt pathway. Apoptosis 22, 437–448 (2017). https://doi.org/10.1007/s10495-016-1326-2

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