Open Access

miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes

  • Authors:
    • Yong‑Lu Pan
    • Zheng‑Yi Han
    • Shu‑Fang He
    • Wan Yang
    • Jie Cheng
    • Ye Zhang
    • Zhi‑Wu Chen
  • View Affiliations

  • Published online on: March 20, 2018     https://doi.org/10.3892/mmr.2018.8784
  • Pages: 7097-7104
  • Copyright: © Pan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In a previous study using a microRNA (miRNA/miR) microarray assay, we demonstrated that miR-133b-5p was upregulated in response to hypoxic preconditioning (HPC). The present study was designed to investigate the role of the miR‑133b‑5p in HPC‑induced cardioprotection and the underlying mechanisms involving caspase‑8 and caspase‑3 apoptotic signaling. Adult rats were subjected to myocardial ischemia/reperfusion (I/R) injury with or without ischemic preconditioning (IPC), and the level of miR‑133b‑5p in myocardium was measured. Neonatal rat cardiomyocytes were isolated and subjected to hypoxia/reoxygenation (H/R) injury, with or without HPC. miR‑133b‑5p antagomir was transfected into the cardiomyocytes to observe whether it could block HPC‑induced cardioprotection. Cellular injury was evaluated by detecting cell viability, lactate dehydrogenase (LDH) activity and apoptotic rate. Reverse transcription‑quantitative polymerase chain reaction was used to measure the level of miR‑133b‑5p. The activation of caspase‑8 and caspase‑3 were measured by western blot analysis to detect the cleaved fragments as well as a colorimetric assay. Following myocardial I/R injury, the expression of miR‑133b‑5p was decreased in myocardium, while this decrease was restored by IPC. HPC protected neonatal rat cardiomyocytes against H/R injury by increasing cell viability, while reducing LDH release and cell apoptosis. These protective effects were coupled with the upregulation of miR‑133b‑5p. However, the knockdown of miR‑133b‑5p in the cardiomyocytes blocked HPC‑mediated cardioprotection as reflected by the aggravation of cell injury and apoptosis. HPC upregulated miR‑133b‑5p level was markedly suppressed by the antagomir. In addition, the cleavage and activities of caspase‑8 and caspase‑3 were inhibited by HPC while reversed by knockdown of miR‑133b‑5p. Upregulation of miR‑133b‑5p contributes to HPC‑mediated cardioprotection in cardiomyocytes, and the mechanism may be associated with inhibition of caspase‑8 and caspase‑3 apoptotic signaling.

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May 2018
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Copy and paste a formatted citation
APA
Pan, Y., Han, Z., He, S., Yang, W., Cheng, J., Zhang, Y., & Chen, Z. (2018). miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes. Molecular Medicine Reports, 17, 7097-7104. https://doi.org/10.3892/mmr.2018.8784
MLA
Pan, Y., Han, Z., He, S., Yang, W., Cheng, J., Zhang, Y., Chen, Z."miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes". Molecular Medicine Reports 17.5 (2018): 7097-7104.
Chicago
Pan, Y., Han, Z., He, S., Yang, W., Cheng, J., Zhang, Y., Chen, Z."miR‑133b‑5p contributes to hypoxic preconditioning‑mediated cardioprotection by inhibiting the activation of caspase‑8 and caspase-3 in cardiomyocytes". Molecular Medicine Reports 17, no. 5 (2018): 7097-7104. https://doi.org/10.3892/mmr.2018.8784