Endothelin-1 and H2O2-induced signaling in vascular smooth muscle cells : modulation by CaMKII and Nitric oxide

摘要: Endothelin-1 has emerged as an extremely potent vasoactive peptide exhibiting mitogenic activity in vascular smooth muscle cells (VSMCs). A critical role of ET-1 many cardiovascular diseases, such atherosclerosis, hypertension, restenosis after angioplasty, heart failure and arrhythmia been suggested. exerts its effects through multiple signaling pathways which include Ca, mitogen-activated protein kinases (MAPKs) including extracellular signal-regulated 1/2 (ERK1/2) phosphatidylinositol 3-kinase (PI-3K)/protein kinase B (PKB)/Akt pathways. Several studies have also demonstrated that reactive oxygen species (ROS) may play important mediating the signals several growth factors peptides hormones linked to these We previously reported generates ROS mediates ET-1-induced signaling. H2O2, molecule, activates both MAPKs PKB VSMCs. In addition, we suggested Ca CaM are essential trigger H2O2-induced ERK1/2, p38 phosphorylation A10 Ca/calmodulin (CaM)-dependent II (CaMKII) is a multifunctional serine/threonine believed transduce downstream Ca/CaM, shown be involved endothelial cells. However, CaMKII H2O2induced PKB, Pyk2 phosphorylation, well effect on hypertrophic proliferative responses VSMCs remains unexplored. Interestingly, diseases showing