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CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury

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 subjec...

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Autores principales: Cai, Wen-Feng, Kang, Kai, Huang, Wei, Liang, Jia-Liang, Feng, Yu-Liang, Liu, Guan-Sheng, Chang, De-Hua, Wen, Zhi-Li, Paul, Christian, Xu, Meifeng, Millard, Ronald W, Wang, Yigang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Ltd 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549033/
https://www.ncbi.nlm.nih.gov/pubmed/25824297
http://dx.doi.org/10.1111/jcmm.12554
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author Cai, Wen-Feng
Kang, Kai
Huang, Wei
Liang, Jia-Liang
Feng, Yu-Liang
Liu, Guan-Sheng
Chang, De-Hua
Wen, Zhi-Li
Paul, Christian
Xu, Meifeng
Millard, Ronald W
Wang, Yigang
author_facet Cai, Wen-Feng
Kang, Kai
Huang, Wei
Liang, Jia-Liang
Feng, Yu-Liang
Liu, Guan-Sheng
Chang, De-Hua
Wen, Zhi-Li
Paul, Christian
Xu, Meifeng
Millard, Ronald W
Wang, Yigang
author_sort Cai, Wen-Feng
collection PubMed
description 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.
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spelling pubmed-45490332015-08-28 CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury Cai, Wen-Feng Kang, Kai Huang, Wei Liang, Jia-Liang Feng, Yu-Liang Liu, Guan-Sheng Chang, De-Hua Wen, Zhi-Li Paul, Christian Xu, Meifeng Millard, Ronald W Wang, Yigang J Cell Mol Med Original Articles 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. John Wiley & Sons, Ltd 2015-08 2015-03-30 /pmc/articles/PMC4549033/ /pubmed/25824297 http://dx.doi.org/10.1111/jcmm.12554 Text en © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. http://creativecommons.org/licenses/by/4.0/ This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Cai, Wen-Feng
Kang, Kai
Huang, Wei
Liang, Jia-Liang
Feng, Yu-Liang
Liu, Guan-Sheng
Chang, De-Hua
Wen, Zhi-Li
Paul, Christian
Xu, Meifeng
Millard, Ronald W
Wang, Yigang
CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
title CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
title_full CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
title_fullStr CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
title_full_unstemmed CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
title_short CXCR4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
title_sort cxcr4 attenuates cardiomyocytes mitochondrial dysfunction to resist ischaemia-reperfusion injury
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549033/
https://www.ncbi.nlm.nih.gov/pubmed/25824297
http://dx.doi.org/10.1111/jcmm.12554
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