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

Tien Yao Tsai, Shyh Liang Lou, Kar Lok Wong, Mei Ling Wang, Tzu Hui Su, Zhong Min Liu, Li Jen Yeh, Paul Chan, Chi Li Gong, Yuk Man Leung

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Release of nitric oxide (NO) is triggered by a rise in endothelial cell (EC) cytosolic Ca2+ concentration ([Ca2+]i) and is of prime importance in vascular tone 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 (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 Ca2+ release; however, they had reduced store-operated Ca2+ entry (SOCE) after LPS 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 Orai1 (two SOCE protein components) in bEND.3 cells treated with LPS for 15 h. 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.

Original languageEnglish
Pages (from-to)80-87
Number of pages8
JournalEuropean Journal of Pharmacology
Volume755
DOIs
Publication statusPublished - May 15 2015

Keywords

  • Endothelial cells
  • Endotoxin
  • NF-κB
  • p38 MAPK
  • Store-operated Ca entry

ASJC Scopus subject areas

  • Pharmacology

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    Tsai, T. Y., Lou, S. L., Wong, K. L., Wang, M. L., Su, T. H., Liu, Z. M., Yeh, L. J., Chan, P., Gong, C. L., & Leung, Y. M. (2015). Suppression of Ca2+ influx in endotoxin-treated mouse cerebral cortex endothelial bEND.3 cells. European Journal of Pharmacology, 755, 80-87. https://doi.org/10.1016/j.ejphar.2015.03.001