1. Academic Validation
  2. Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases

Fas/CD95/Apo-I activates the acidic sphingomyelinase via caspases

  • Cell Death Differ. 1998 Jan;5(1):29-37. doi: 10.1038/sj.cdd.4400307.
B Brenner 1 K Ferlinz H Grassmé M Weller U Koppenhoefer J Dichgans K Sandhoff F Lang E Gulbins
Affiliations

Affiliation

  • 1 Department of Physiology, University of Tuebingen, Gmelinstrasse 5, 72076 Tuebingen, Germany.
Abstract

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.

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