title: Inhibiting (pro)renin receptor-mediated p38 MAPK signaling decreases hypoxia/reoxygenation-induced apoptosis in H9c2 cells.
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.
authors.affiliation: Department of Cardiology, The 1st Affiliated Hospital of Dalian Medical University, Lianhe Road No. 193, Shahekou District, Dalian, Liaoning, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Shenglin
authors.initials: S
authors.lastname: Zhang
authors.forename: Dechun
authors.initials: D
authors.lastname: Su
authors.forename: Jinqiu
authors.initials: J
authors.lastname: Liu
authors.forename: Yunpeng
authors.initials: Y
authors.lastname: Cheng
authors.forename: Lu
authors.initials: L
authors.lastname: Zou
authors.forename: Wenqiang
authors.initials: W
authors.lastname: Li
authors.forename: Yinong
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D055785:Gene Knockdown Techniques; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010100:Oxygen / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000093342:Prorenin Receptor
chemical_list: D007093:Imidazoles; D011725:Pyridines; D034741:RNA, Small Interfering; D011956:Receptors, Cell Surface; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3; C093642:SB 203580; D010100:Oxygen; D000093342:Prorenin Receptor