N,N-Dimethyl-D-erythro-sphingosine inhibits store-operated Ca2+ entry in U937 monocytes.
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 Ca(2+) 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 Mn(2+)-quenching method, which monitors only Ca(2+) 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-beta-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 Ca(2+) concentration by sphingolipids, although the precise mechanism should be elucidated in the future.
Jo
Ji-Yeong
JY
Laboratory of Pharmacology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Busan, Korea.
Kim
Hyo-Lim
HL
Lee
Yun-Kyung
YK
Tomura
Hideaki
H
Bae
Yoe-Sik
YS
Okajima
Fumikazu
F
Im
Dong-Soon
DS
D006801:Humans; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D020298:U937 Cells
C061800:N,N-dimethylsphingosine; D013110:Sphingosine