CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia‐reperfusion injury

Journal of Cellular and Molecular Medicine

Wen-Feng Cai²  Kai Kang²  Wei Huang²  Jia-Liang Liang²  Yu-Liang Feng²  Guan-Sheng Liu¹  De-Hua Chang²  Zhi-Li Wen²  Christian Paul²  Meifeng Xu²  Ronald W. Millard¹ 

[1] Department of Pharmacology & Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati, OH, USA;Department of Pathology & Lab Medicine, College of Medicine, University of Cincinnati, Cincinnati, OH, USA

关键词: CXCR4 overexpression;    ischaemia/reperfusion injury;    mitochondria;    cardiomyocytes;    STAT3;   

DOI  :  10.1111/jcmm.12554

来源: Wiley

【 摘 要 】

Abstract

The chemokine (C-X-C motif) receptor 4 (CXCR4) is expressed on native cardiomyocytes and can modulate isolated cardiomyocyte contractility. This study examines the role of CXCR4 in cardiomyocyte response to ischaemia-reperfusion (I/R) injury. Isolated adult rat ventricular cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) to simulate I/R injury. In response to H/R injury, the decrease in CXCR4 expression was associated with dysfunctional energy metabolism indicated by an increased adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio. CXCR4-overexpressing cardiomyocytes were used to determine whether such overexpression (OE) can prevent bio-energetic disruption-associated cell death. CXCR4 OE was performed with adenoviral infection with CXCR4 encoding-gene or non-translated nucleotide sequence (Control). The increased CXCR4 expression was observed in cardiomyocytes post CXCR4-adenovirus transduction and this OE significantly reduced the cardiomyocyte contractility under basal conditions. Although the same extent of H/R-provoked cytosolic calcium overload was measured, the hydrogen peroxide-induced decay of mitochondrial membrane potential was suppressed in CXCR4 OE group compared with control group, and the mitochondrial swelling was significantly attenuated in CXCR4 group, implicating that CXCR4 OE prevents permeability transition pore opening exposure to overload calcium. Interestingly, this CXCR4-induced mitochondrial protective effect is associated with the enhanced signal transducer and activator of transcription 3 (expression in mitochondria. Consequently, in the presence of H/R, mitochondrial dysfunction was mitigated and cardiomyocyte death was decreased to 65% in the CXCR4 OE group as compared with the control group. I/R injury leads to the reduction in CXCR4 in cardiomyocytes associated with the dysfunctional energy metabolism, and CXCR4 OE can alleviate mitochondrial dysfunction to improve cardiomyocyte survival.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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