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Inhibiting (pro)renin receptor-mediated p38 MAPK signaling decreases hypoxia/reoxygenation-induced apoptosis in H9c2 cells

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Abstract

The (pro)renin receptor is a new molecular member of the renin–angiotensin system and participates in regulating many physiological and pathological processes. However, the role of (pro)renin receptor-mediated signaling pathways in myocardial ischemic/reperfusion injury remains unclear. In this study, we hypothesized that p38 mitogen-activated protein kinase (MAPK) signaling pathway activation by the (pro)renin receptor had effects on myocardial apoptosis induced by ischemia/reperfusion. This analysis was performed using a hypoxia/reoxygenation model in H9c2 cells to mimic ischemia/reperfusion injury. The H9c2 rat cardiomyocyte cell line was subjected to 2 h of hypoxia followed by 6 h of reoxygenation. The (pro)renin receptor, caspase 3, and phosphorylated p38 MAPK protein expression levels were analyzed by Western blot. After 2 h of hypoxia followed by 6 h of reoxygenation, apoptosis increased in H9c2 cells; the (pro)renin receptor, caspase 3, and phosphorylated p38 MAPK protein expressions were upregulated. siRNA silencing of the (pro)renin receptor significantly decreased p38 MAPK phosphorylation. siRNA silencing of the (pro)renin receptor and treatment with the p38MAPK inhibitor SB203580 significantly decreased the hypoxia/reoxygenation-induced apoptosis and caspase 3 protein expression in H9c2 cells. Furthermore, we found that the role of the (pro)renin receptor was independent of angiotensin II (Ang II). Thus, we concluded that (pro)renin receptor activation could trigger hypoxia/reoxygenation-induced apoptosis in H9c2 cells, partially through the p38 MAPK/caspase 3 signaling pathway, independent of Ang II. Therefore, this study may provide new therapeutic targets for myocardial ischemic/reperfusion injury prevention, and further in vivo studies are needed.

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Conflict of interest

The authors have no conflicts of interest to declare.

Funding

This work was supported by the National Natural Science Foundation of China (No. 3027143).

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Authors and Affiliations

  1. Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China

    Yan Liu, Shenglin Zhang, Dechun Su, Jinqiu Liu, Yunpeng Cheng & Yinong Jiang

  2. Dalian Medical University, Liaoning, China

    Lu Zou & Wenqiang Li

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  1. Yan Liu
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  2. Shenglin Zhang
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  3. Dechun Su
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  4. Jinqiu Liu
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Correspondence to Yinong Jiang.

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Liu, Y., Zhang, S., Su, D. et al. Inhibiting (pro)renin receptor-mediated p38 MAPK signaling decreases hypoxia/reoxygenation-induced apoptosis in H9c2 cells. Mol Cell Biochem 403, 267–276 (2015). https://doi.org/10.1007/s11010-015-2356-8

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  • DOI: https://doi.org/10.1007/s11010-015-2356-8

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