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Prohibitin protects against oxidative stress-induced cell injury in cultured neonatal cardiomyocyte

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Cell Stress and Chaperones Aims and scope

Abstract

Oxidative stress is one of the main causes of myocardial injury, which is associated with cardiomyocyte death. Mitochondria play a key role in triggering the necrosis and apoptosis pathway of cardiomyocytes under oxidative stress. Although prohibitin (PHB) has been acknowledged as a mitochondrial chaperone, its functions in cardiomyocytes are poorly characterized. The present research was designed to investigate the cardioprotective role of PHB in mitochondria. Oxidative stress can increase the PHB content in mitochondria in a time-dependent manner. Overexpression of PHB in cultured cardiomyocytes by transfection of recombinant adenovirus vector containing PHB sense cDNA resulted in an increase of PHB in mitochondria. Compared with the non-transfection cardiomyocytes, PHB overexpression could protect the mitochondria from oxidative stress-induced injury. The mitochondria-mediated apoptosis pathway was consistently suppressed in PHB-overexpressed cardiomyocytes after hydrogen peroxide (H2O2) treatment, including a reduced change in mitochondrial membrane permeability transition and an inhibited release of cytochrome c from mitochondria to cytoplasma. As a result, the oxidative stress-induced cardiomyocyte apoptosis was suppressed. These data indicated that PHB protected the cardiomyocytes from oxidative stress-induced damage, and that increasing PHB content in mitochondria constituted a new therapeutic target for myocardium injury.

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Abbreviations

PHB:

prohibitin

MEM:

modified Eagle’s medium

Cox II:

cytochrome c oxidase subunit II

LDH:

lactate dehydrogenase

CK:

creatine kinase

MMP:

mitochondrial transmembrane potential

MPTP:

membrane permeability transition pore

H2O2 :

hydrogen peroxide

PBS:

phosphate-buffered saline

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Acknowledgments

This research was supported by the General Program of the Chinese National Natural Science Foundation (grant no. 30570753) and the Major Research Plan of the Chinese National Natural Science Foundation (grant nos. 30430590 and 30393134).

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Authors and Affiliations

  1. Department of Stress Medicine, Institute of Health & Environmental Medicine, DaLi Road 1, Tianjin, 300050, People’s Republic of China

    XiaoHua Liu, Zhe Ren, Rui Zhan, XinXing Wang, XiaoMing Wang, ZhiQing Zhang, Xue Leng, ZhiHua Yang & LingJia Qian

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  1. XiaoHua Liu
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  2. Zhe Ren
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Corresponding author

Correspondence to LingJia Qian.

Additional information

XiaoHua Liu and Zhe Ren contributed equally to this work.

● Prohibitin is an evolutionarily conserved and ubiquitously expressed protein involved in mitochondrial structure, function, and inheritance whose function in cardiomyocyte is not known. In this study, we found oxidative stress could induce increased expression in cardiomyocytes and mitochondrial translocation of PHB, and PHB can protect against oxidative stress in cultured neonatal cardiomyocyte.

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Liu, X., Ren, Z., Zhan, R. et al. Prohibitin protects against oxidative stress-induced cell injury in cultured neonatal cardiomyocyte. Cell Stress and Chaperones 14, 311–319 (2009). https://doi.org/10.1007/s12192-008-0086-5

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  • DOI: https://doi.org/10.1007/s12192-008-0086-5

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