Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases
| Autor: | Michael Weller, Klaus Ferlinz, Florian Lang, Brigit Brenner, Erich Gulbins, Johannes Dichgans, Konrad Sandhoff, Ursula Koppenhoefer, Heike Grassmé |
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| Předmět: |
Ceramide
Imipramine p38 mitogen-activated protein kinases T-Lymphocytes Stimulation Apoptosis Cysteine Proteinase Inhibitors Ceramides Transfection p38 Mitogen-Activated Protein Kinases Gene Expression Regulation Enzymologic Amino Acid Chloromethyl Ketones Diglycerides chemistry.chemical_compound Jurkat Cells Viral Proteins Humans fas Receptor Molecular Biology Caspase Serpins biology Adrenergic Uptake Inhibitors Cell Biology Fas receptor Cell biology Sphingomyelin Phosphodiesterase chemistry Caspases Calcium-Calmodulin-Dependent Protein Kinases biology.protein Mitogen-Activated Protein Kinases Sphingomyelin Acids Signal Transduction |
| Zdroj: | Scopus-Elsevier |
| Popis: | Fas/CD95/Apo-I has been shown to stimulate a variety of molecules including several members of the caspase family and the acidic sphingomyelinase (Martin and Green 1995; Gulbins et al, 1995). Here, we demonstrate that Fas receptor-triggered activation of the acidic sphingomyelinase, consumption of sphingomyelin, release of ceramide, and subsequent activation of JNK and p38-K are regulated by caspases. Inhibition of caspases by Ac-YVAD-chloromethylketone or transient CrmA transfection prevented stimulation of acidic sphingomyelinase, release of ceramide and activation of JNK and p38-K upon Fas-receptor crosslinking. Likewise, Fas triggered apoptosis was almost completely blocked by Ac-YVAD-chloromethylketone or CrmA mediated inhibition of caspases. The results suggest a new signalling cascade from the Fas receptor via caspases to acidic sphingomyelinase, ceramide and JNK/p38-K. |
| Databáze: | OpenAIRE |
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