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

2 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

Fingerprint

Endotoxins
Cerebral Cortex
Lipopolysaccharides
p38 Mitogen-Activated Protein Kinases
Endothelial Cells
Ion Channels
Nitric Oxide
Sodium Salicylate
Vascular Smooth Muscle
Critical Illness
Blood Vessels
Real-Time Polymerase Chain Reaction
Sepsis
Hemodynamics
Cell Membrane
Gene Expression
Proteins

Keywords

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

ASJC Scopus subject areas

  • Pharmacology

Cite this

Tsai, T. Y., Lou, S. L., Wong, K. L., Wang, M. L., Su, T. H., Liu, Z. M., ... 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

Suppression of Ca2+ influx in endotoxin-treated mouse cerebral cortex endothelial bEND.3 cells. / Tsai, Tien Yao; Lou, Shyh Liang; Wong, Kar Lok; Wang, Mei Ling; Su, Tzu Hui; Liu, Zhong Min; Yeh, Li Jen; Chan, Paul; Gong, Chi Li; Leung, Yuk Man.

In: European Journal of Pharmacology, Vol. 755, 15.05.2015, p. 80-87.

Research output: Contribution to journalArticle

Tsai, Tien Yao ; Lou, Shyh Liang ; Wong, Kar Lok ; Wang, Mei Ling ; Su, Tzu Hui ; Liu, Zhong Min ; Yeh, Li Jen ; Chan, Paul ; Gong, Chi Li ; Leung, Yuk Man. / Suppression of Ca2+ influx in endotoxin-treated mouse cerebral cortex endothelial bEND.3 cells. In: European Journal of Pharmacology. 2015 ; Vol. 755. pp. 80-87.
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