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

Journal of Pharmacological Sciences

Hideaki Tomura³  Ji-Yeong Jo²  Fumikazu Okajima³  Dong-Soon Im²  Yoe-Sik Bae¹  Yun-Kyung Lee²  Hyo-Lim Kim² 

[1] Department of Biochemistry, College of Medicine, Dong-A University, Korea;Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Korea;Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Japan

关键词: dimethylsphingosine;    dimethylphytosphingosine;    sphingosine;    store-operated Ca2+ entry;    calcium;   

DOI  :  10.1254/jphs.08078FP

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(24)Cited-By(1)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.

【 授权许可】

Unknown