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NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2

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Abstract

Angiotensin II(Ang II)-stimulated cardiomyocytes hypertrophy and apoptosis are associated with nuclear factor-κB (NF-κB) activation. NF-κB, a redox-sensitive transcription factor, contributes a critical role in cell death, but, Ang II-stimulated NF-κB-mediated cardiomyocytes apoptosis remains less understood. Recently, microRNAs (miRNAs) have been shown to be critical regulators in various cardiac remodeling processes; however, NF-κB-mediated miRNA’s role in cardiomyocytes apoptosis remains undetermined. The miR-30b has been implicated in diverse cardiac remodeling; but, NF-κB-mediated miR-30b modulation in Ang II-induced cardiomyocytes death is currently unknown. In the present study, neonatal cardiomyocytes were pretreated with SN50, a selective cell permeable peptide inhibitor of NF-κB, or transfected with miR-30b mimetic and inhibitors separately, and then challenged with Ang II. The target gene, Bcl-2, and NF-κB transcriptional activity were analyzed. Our results demonstrated that NF-κB positively regulated miR-30b expression in Ang II-induced cardiomyocytes apoptosis, and Bcl-2 was a direct target for miR-30b. NF-κB further regulated the expression of Bcl-2 in the above setting. Furthermore, Ang II-induced cardiomyocytes apoptosis rescued by inhibiting either NF-κB or miR-30b provided an important role in cardiomyocytes cell death. We evaluated a critical role of NF-κB-mediated miR-30b modulation in Ang II-stimulated cardiomyocytes targeting Bcl-2. Our data may provide a new insight of miR-30b’s role in myocardial infarction or ischemia.

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Acknowledgments

This study was partly supported by start-up funds from the Texas A&M Health Science Center, College of Medicine, by an American Heart Association-National Scientist Development Grant (0835227N) to S. Gupta (SG). The authors also acknowledge to Central Texas Veterans Affairs Health Care System for providing research facility to complete this work.

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Authors and Affiliations

  1. Division of Molecular Cardiology, Department of Medicine, College of Medicine, Texas A & M Health Science Center, Temple, TX, USA

    Chuanyu Wei, Li Li & Sudhiranjan Gupta

  2. Scott & White, Temple, TX, USA

    Chuanyu Wei, Li Li & Sudhiranjan Gupta

  3. Central Texas Veterans Health Care System, Temple, TX, USA

    Chuanyu Wei, Li Li & Sudhiranjan Gupta

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  1. Chuanyu Wei
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  2. Li Li
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Correspondence to Sudhiranjan Gupta.

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Wei, C., Li, L. & Gupta, S. NF-κB-mediated miR-30b regulation in cardiomyocytes cell death by targeting Bcl-2. Mol Cell Biochem 387, 135–141 (2014). https://doi.org/10.1007/s11010-013-1878-1

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  • DOI: https://doi.org/10.1007/s11010-013-1878-1

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