title: Suppression of Ca(2+) influx in endotoxin-treated mouse cerebral cortex endothelial bEND.3 cells.
abstract: Release of nitric oxide (NO) is triggered by a rise in endothelial cell (EC) cytosolic Ca(2+) concentration ([Ca(2+)]i) and is of prime importance in vascular tone regulation as NO relaxes vascular smooth muscle. Agonists could stimulate EC [Ca(2+)]i elevation by triggering Ca(2+) influx via plasma membrane ion channels, one of which is the store-operated Ca(2+) channel; the latter opens as a result of agonist-triggered internal Ca(2+) release. Endotoxin (lipopolysaccharide, LPS) could cause sepsis, which is often the fatal cause in critically ill patients. One of the LPS-induced damages is EC dysfunction, eventually leading to perturbations in hemodynamics. We obtained data showing that LPS-challenged mouse cerebral cortex endothelial bEND.3 cells did not suffer from apoptotic death, and in fact had intact agonist-triggered intracellular Ca(2+) release; however, they had reduced store-operated Ca(2+) entry (SOCE) after LPS treatment for 3h or more. Using real-time PCR, we did not find a decrease in gene expression of stromal interaction molecule 1 (STIM1) and Orai1 (two SOCE protein components) in bEND.3 cells treated with LPS for 15h. LPS inhibitory effects could be largely prevented by sodium salicylate (an inhibitor of nuclear factor-κB; NF-κB) or SB203580 (an inhibitor of p38 mitogen-activated protein kinases; p38 MAPK), suggesting that the p38 MAPK-NF-κB pathway is involved in SOCE inhibition.
authors.affiliation: Cardiovascular Division, Lotung Poh-Ai Hospital, Luodong, Taiwan; Department of Biomedical Engineering, Chung Yuan Christian University, Chungli, Taiwan.
authors.forename: Tien-Yao
authors.initials: TY
authors.lastname: Tsai
authors.affiliation: Department of Biomedical Engineering, Chung Yuan Christian University, Chungli, Taiwan.
authors.forename: Shyh-Liang
authors.initials: SL
authors.lastname: Lou
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Kar-Lok
authors.initials: KL
authors.lastname: Wong
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Tzu-Hui
authors.initials: TH
authors.lastname: Su
authors.affiliation: Department of Cardiovascular Surgery, Shanghai East Hospital, Tongji University, Shanghai, China.
authors.forename: Zhong-Min
authors.initials: ZM
authors.lastname: Liu
authors.affiliation: Department of Anesthesiology, Eda Hospital and I-Shou University, Kaohsiung, Taiwan.
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Yeh
authors.affiliation: Division of Cardiology, Department of Medicine, Taipei Medical University Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Paul
authors.initials: P
authors.lastname: Chan
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan.
authors.forename: Chi-Li
authors.initials: CL
authors.lastname: Gong
authors.affiliation: Department of Physiology, China Medical University, Taichung, Taiwan. Electronic address: ymleung@mail.cmu.edu.tw.
authors.forename: Yuk-Man
authors.initials: YM
authors.lastname: Leung
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D000071740:ORAI1 Protein; D000071737:Stromal Interaction Molecule 1; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071740:ORAI1 Protein; C520430:Orai1 protein, mouse; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D002118:Calcium
keywords: Endothelial cells; Endotoxin; NF-κB; Store-operated Ca(2+) entry; p38 MAPK