Sphingosine-1-phosphate-induced intracellular Ca2+ mobilization in human endothelial cells

Geun Hee Seol, Moon Y. Kim, Guo Hua Liang, Ji Aee Kim, Young Ju Kim, Seikwan Oh, Suk Hyo Suh

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12 Scopus citations


The authors have studied the effect of sphingosine-1-phosphate (S1P) on Ca2+ release from intracellular stores in cultured human umbilical vein endothelial cells (HUVECs). In the presence of extracellular Ca2+, S1P increased intracellular Ca2+ concentration ([Ca2+]i) and this increase was partially inhibited by La3+ (1 μM), indicating that S1P induces Ca2+ influx from extracellular pool and Ca2+ release from intracellular stores. S1P increased [Ca2+]i concentration dependently in Ca2+-free extracellular solution. The Hill coefficient (1.7) and EC50 (420 nM) was obtained from the concentration-response relationship. When caffeine depleted Ca2+ store in the presence of ryanodine, S1P did not induce intracellular Ca2+ release. Furthermore, the Ca2+-induced Ca2+ release inhibitors ruthenium red or dantrolene completely inhibited S1P-induced intracellular Ca2+ release. S1P-induced intracellular Ca2+ release was inhibited by the phospholipase C (PLC) inhibitors neomycin and U73312, or the inositol 1,4,5-triphosphate (IP3)-gated Ca2+ channel blocker aminoethoxybiphenyl borane (2-APB). In contrast, S1P-induced intracellular Ca2+ release was not inhibited by the mitochondrial Ca2+ uptake inhibitor CCCP or the mitochondrial Ca2+ release inhibitor cyclosporin A. These results show that S1P mobilizes Ca 2+ from intracellular stores primarily via Ca2+-induced and IP3-induced Ca 2+ release and this Ca2+ mobilization is independent of mitochondrial Ca2+ stores.

Original languageEnglish
Pages (from-to)263-269
Number of pages7
JournalEndothelium: Journal of Endothelial Cell Research
Issue number5-6
StatePublished - Sep 2005

Bibliographical note

Funding Information:
Received 1 August 2005; accepted 18 October 2005. This work was supported by the Korean Science and Engineering Foundation (no. R01-2003-000-10466-0). Address correspondence to Suk Hyo Suh, Department of Physiology, College of Medicine, Ewha Women’s University, 911-1 Mok-6-dong, Yang Chun-gu, Seoul, Republic of Korea, 158-710. E-mail: [email protected]


  • Ca-induced Ca release
  • Human umbilical vein endothelial cells
  • IP-induced Ca release
  • Sphingosine-1-phosphate


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