Document Detail

Effects of synthetic sphingosine-1-phosphate analogs on arachidonic acid metabolism and cell death.
MedLine Citation:
PMID:  15498509     Owner:  NLM     Status:  MEDLINE    
Sphingolipid metabolites such as sphingosine regulate cell functions including cell death and arachidonic acid (AA) metabolism. D-erythro-C18-Sphingosine-1-phosphate (D-e-S1P), a sphingolipid metabolite, acts as an intracellular messenger in addition to being an endogenous ligand of some cell surface receptors. The development of S1P analogs may be useful for studying and/or regulating S1P-mediated cellular responses. In the present study, we found that several synthetic S1P analogs at pharmacological concentrations stimulated AA metabolism and cell death in PC12 cells. D-erythro-N,O,O-Trimethyl-C18-S1P (D-e-TM-S1P), L-threo-O,O-dimethyl-C18-S1P (L-t-DM-S1P) and L-threo-O,O-dimethyl-3O-benzyl-C18-S1P (L-t-DMBn-S1P) at 100 microM stimulated [(3)H]AA release from the prelabeled PC12 cells. L-t-DMBn-S1P at 20 microM increased prostanoid formation in PC12 cells. L-t-DMBn-S1P-induced AA release was inhibited by D-e-sphingosine, but not by the tested PLA(2) inhibitors. L-t-DMBn-S1P did not stimulate the activity of cytosolic phospholipase A(2alpha) (cPLA(2alpha)) in vitro and the translocation of cPLA(2alpha) in the cells, and caused AA release from the cells lacking cPLA(2alpha). These findings suggest that L-t-DMBn-S1P stimulated AA release in a cPLA(2alpha)-independent manner. In contrast, D-e-S1P and D-erythro-N-monomethyl-C18-S1P caused cell death without AA release in PC12 cells, and the effects of D-e-TM-S1P, L-t-DM-S1P and L-t-DMBn-S1P on cell death were limited. Synthetic S1P analogs may be useful tools for studying AA metabolism and cell death in cells.
Hiroyuki Nakamura; Yuko Takashiro; Tetsuya Hirabayashi; Syunji Horie; Yuuki Koide; Atsushi Nishida; Toshihiko Murayama
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical pharmacology     Volume:  68     ISSN:  0006-2952     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-10-22     Completed Date:  2005-02-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  2187-96     Citation Subset:  IM    
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 263-8522, Japan.
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MeSH Terms
Arachidonic Acid / metabolism*
Cell Death / drug effects*
Lysophospholipids / chemical synthesis,  chemistry,  pharmacology*
PC12 Cells
Phospholipases A / metabolism
Sphingosine / analogs & derivatives*,  chemical synthesis,  chemistry,  pharmacology*
Reg. No./Substance:
0/Lysophospholipids; 123-78-4/Sphingosine; 26993-30-6/sphingosine 1-phosphate; 506-32-1/Arachidonic Acid; EC 3.1.1.-/Phospholipases A

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