Suppression of Ca2+ influx in endotoxin-treated mouse cerebral cortex endothelial bEND.3 cells

摘要

Release of nitric oxide (NO) is triggered by a rise in endothelial cell (EC) cytosolic Ca2+ concentration (ICa2+)(i) and is of prime importance in vascular Lone regulation as NO relaxes vascular smooth muscle. Agonists could stimulate EC [Ca2+](i) elevation by triggering Ca2+ influx via plasma membrane ion channels, one of which is the store operated Ca2+ channel; the latter opens as a result of agonist-triggered internal Ca2+ release. Endotoxin (lipopolysaccharicle, [PS) could cause sepsis, which is often the fatal cause in critically ill patients. One of the [PS-induced damages is EC dysfunction, eventually leading to perturbations in hemodynamics. We obtained data showing that [PS-challenged mouse cerebral cortex endothelial bEND.3 cells did not suffer from apoptotic death, and in fact had intact agonist-triggered intracellular Ca2+ release; however, they had reduced store-operated Ca2+ entry (SOCE) after [PS treatment for 3 h or more. Using real-time PCR, we did not find a decrease in gene expression of stromal interaction molecule 1 (STIM1) and Orail (two SOCE protein components) in bEND.3 cells treated with [PS for 15 h. [PS inhibitory effects could be largely prevented by sodium salicylate (an inhibitor of nuclear factor-kappa B; NE-kappa B) or SB203580 (an inhibitor of p38 mitogen-activated protein kinases; p38 EVAPK), suggesting that the p38 MAPK-NF-kappa B pathway is involved in SOCE inhibition. (C) 2015 Elsevier BM. All rights reserved.