caa a22 4500 606236716 CHVBK 20210128101249.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s11010-015-2356-8 doi (NATIONALLICENCE)springer-10.1007/s11010-015-2356-8 Inhibiting (pro)renin receptor-mediated p38 MAPK signaling decreases hypoxia/reoxygenation-induced apoptosis in H9c2 cells [Elektronische Daten] [Yan Liu, Shenglin Zhang, Dechun Su, Jinqiu Liu, Yunpeng Cheng, Lu Zou, Wenqiang Li, Yinong Jiang] 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 2h of hypoxia followed by 6h of reoxygenation. The (pro)renin receptor, caspase 3, and phosphorylated p38 MAPK protein expression levels were analyzed by Western blot. After 2h of hypoxia followed by 6h 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. Springer Science+Business Media New York, 2015 H9c2 cell apoptosis nationallicence Hypoxia/reoxygenation nationallicence p38 MAPK nationallicence (pro)renin receptor nationallicence Liu Yan Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut Zhang Shenglin Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut Su Dechun Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut Liu Jinqiu Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut Cheng Yunpeng Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut Zou Lu Dalian Medical University, Liaoning, China aut Li Wenqiang Dalian Medical University, Liaoning, China aut Jiang Yinong Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 267-276 0300-8177 403:1-2<267 2015 403 11010 https://doi.org/10.1007/s11010-015-2356-8 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-015-2356-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Liu Yan Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut NATIONALLICENCE 700 1- Zhang Shenglin Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut NATIONALLICENCE 700 1- Su Dechun Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut NATIONALLICENCE 700 1- Liu Jinqiu Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut NATIONALLICENCE 700 1- Cheng Yunpeng Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut NATIONALLICENCE 700 1- Zou Lu Dalian Medical University, Liaoning, China aut NATIONALLICENCE 700 1- Li Wenqiang Dalian Medical University, Liaoning, China aut NATIONALLICENCE 700 1- Jiang Yinong Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 403/1-2(2015-05-01), 267-276 0300-8177 403:1-2<267 2015 403 11010