N,N-Dimethyl-<sc><font size = "-2">D</font></sc>-erythro-Sphingosine Inhibits Store-Operated Ca2+ Entry in U937 Monocytes

Ji-Yeong Jo; Hyo-Lim Kim; Yun-Kyung Lee; Hideaki Tomura; Yoe-Sik Bae; Fumikazu Okajima; Dong-Soon Im

doi:10.1254/jphs.08078FP

Full Papers

N,N-Dimethyl-D-erythro-Sphingosine Inhibits Store-Operated Ca²⁺ Entry in U937 Monocytes

Ji-Yeong Jo, Hyo-Lim Kim, Yun-Kyung Lee, Hideaki Tomura, Yoe-Sik Bae, Fumikazu Okajima, Dong-Soon Im

Author information

Ji-Yeong Jo
Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Korea
Hyo-Lim Kim
Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Korea
Yun-Kyung Lee
Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Korea
Hideaki Tomura
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Japan
Yoe-Sik Bae
Department of Biochemistry, College of Medicine, Dong-A University, Korea
Fumikazu Okajima
Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Japan
Dong-Soon Im
Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Korea

Keywords: dimethylsphingosine, dimethylphytosphingosine, sphingosine, store-operated Ca²⁺ entry, calcium

JOURNAL FREE ACCESS

2008 Volume 107 Issue 3 Pages 303-307

DOI https://doi.org/10.1254/jphs.08078FP

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Abstract

Calcium is a ubiquitous second messenger that controls a broad range of cellular functions, and store-operated calcium entry (SOCE) is the primary mechanism of regulated Ca²⁺ entry in non-excitable immunocytes. In this study, we found that N,N-dimethyl-D-erythro-sphingosine (DMS) inhibited SOCE. In U937 cells, treatment with DMS for 2 h inhibited thapsigargin-induced SOCE by about 70%. DMS inhibited SOCE in a concentration-dependent manner when it was added to the cells after SOCE reached a plateau. DMS-induced SOCE inhibition was also confirmed by the Mn²⁺-quenching method, which monitors only Ca²⁺ influx. Because sphingosine kinase inhibitors or protein kinase C (PKC) inhibitors could not mimic the SOCE inhibition, sphingosine kinase and PKC could be excluded as targets of DMS-induced inhibition of SOCE. Furthermore, disruption of lipid rafts with methyl-β-cyclodextrin and bacterial sphingomyelinase did not influence DMS-induced inhibition of SOCE. DMS-induced inhibition of SOCE in U937 human monocytes is a unique observation and could serve as a basis to study modulation of intracellular Ca²⁺ concentration by sphingolipids, although the precise mechanism should be elucidated in the future.

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