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MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway

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Abstract

Myocardial ischemia reperfusion (I/R) can induce altered expression of microRNAs (miRNAs). The miRNAs—miR-15a, miR-15b and miR-16 have been shown to play a role in apoptosis, although not in cardiac-related models. We investigated the roles of miR-15b in hypoxia/reoxygenation (H/R)-induced apoptosis of cardiomyocytes. Quantitative real time polymerase chain reaction results showed that the expression of miR-15a and miR-15b were up-regulated in Sprague–Dawley rat hearts subjected to I/R. Expression levels of miR-15b increased more than four fold above basal levels. Similar results were obtained for cardiomyocytes exposed to H/R. Recombinant adenoviral vectors were generated to explore the functional role of miR-15b in cultured cardiomyocytes exposed to H/R. Overexpression of miR-15b enhanced cell apoptosis and the loss of mitochondrial membrane potential, as determined by flow cytometric analysis. Conversely, down-regulated expression was cytoprotective. The effects of miR-15b can by mimicked by Bcl-2 short-interfering RNAs. The inhibition of miR-15b increased expression levels of the Bcl-2 protein without affecting Bcl-2 mRNA levels, suppressed the release of mitochondrial cytochrome c to the cytosol and decreased the activities of caspase-3 and 9. It is possible that miR-15b is the upstream regulator of a mitochondrial signaling pathway for H/R induced apoptosis.

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Authors and Affiliations

  1. Department of Geriatric Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Lifeng Liu, Jing Bai & Yu Wang

  2. Department of Cardiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Zhuo Liang & Tiande Li

  3. Department of Pathophysiology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing, 100853, China

    Xiuhua Liu

  4. State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27 Taiping Road, Beijing, 100850, China

    Jiao Fan

  5. Department of Cardiology, The General Hospital of Jinan Military Command, Jinan, China

    Guoming Zhang

Authors
  1. Lifeng Liu
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  2. Guoming Zhang
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  3. Zhuo Liang
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  4. Xiuhua Liu
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  5. Tiande Li
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  6. Jiao Fan
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  7. Jing Bai
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  8. Yu Wang
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Corresponding author

Correspondence to Yu Wang.

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Lifeng Liu and Guoming Zhang authors contributed equally to this work.

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Liu, L., Zhang, G., Liang, Z. et al. MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway. Apoptosis 19, 19–29 (2014). https://doi.org/10.1007/s10495-013-0899-2

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  • DOI: https://doi.org/10.1007/s10495-013-0899-2

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