Sphingolipid metabolism and signal transduction: inhibition of in vitro phospholipase activity by sphingosine
| Autor: | Richard C. Franson, Miriam D. Rosenthal, Shobha Ghosh, Lesley K. Harris |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Ceramide
Octoxynol Phospholipase Binding Competitive Phospholipases A Polyethylene Glycols Substrate Specificity chemistry.chemical_compound Phospholipase A2 Sphingosine Phospholipase D Animals Humans Phospholipase D activity Molecular Biology Sphingolipids biology Cell Biology Sphingolipid chemistry Biochemistry biology.protein Sphingomyelin Signal Transduction |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1136:169-174 |
| ISSN: | 0167-4889 |
| Popis: | Sphingosine inhibits protein kinase C activity in vitro and has been used to implicate this enzyme in signal transduction and cell function. We report that sphingosine directly inhibits phospholipases A2 and D. Sphingosine inhibits Ca(2+)-dependent phospholipases A2 from Naja naja, porcine pancreas, Crotalus adamanteus, human disc and neutrophil in a dose-dependent manner with IC50 values ranging from 5-40 microM using [1-14C]oleate-labelled autoclaved E. coli (20 microM) as substrate. Inhibition is comparable using the same concentrations (20 microM) of [1-14C]oleate-labelled C. albicans or E. coli, or aqueous dispersions of 1-acyl-2-[1-14C]linoleoylglycerophosphoethanolamine or -choline. Sphinganine and stearylamine are as inhibitory as sphingosine; monoolein is less inhibitory (IC50 = 70 microM), while octylamine, N-acetylsphingosine, sphingomyelin and ceramide have no effect. Inhibition is relieved by increasing concentrations of substrate phospholipid. The molar ratio of sphingosine to phospholipid required for 50% inhibition ranges from 0.5 to 1.0 with 2-100 microM E. coli phospholipid. In contrast, sphingosine has a biphasic effect on the hydrolysis of E. coli by S. chromofuscus phospholipase D; concentrations less than or equal to 25 microM stimulate activity while concentrations greater than 25 microM are inhibitory. Addition of Triton X-100 eliminates both the stimulatory and inhibitory effects of sphingosine on phospholipase D activity. |
| Databáze: | OpenAIRE |
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