Fas/CD95/Apo-I activates the acidic sphingomyelinase via Caspases (original) (raw)

• Original Paper
• Published: 28 January 1998
• Klaus Ferlinz2,
• Heike Grassmé1,
• Michael Weller3,
• Ursula Koppenhoefer1,
• Johannes Dichgans3,
• Konrad Sandhoff2,
• Florian Lang1 &
• …
• Erich Gulbins1

Cell Death & Differentiation volume 5, pages 29–37 (1998)Cite this article

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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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Authors and Affiliations

1. Department of Physiology, University of Tuebingen, Gmelinstrasse 5, Tuebingen, 72076, Germany
   Brigit Brenner, Heike Grassmé, Ursula Koppenhoefer, Florian Lang & Erich Gulbins
2. Department of Organic Chemistry and Biochemistry, University of Bonn, Gerhard Domagk-Str. 1, Bonn, 53121, Germany
   Klaus Ferlinz & Konrad Sandhoff
3. Department of Neurology, University of Tuebingen, Tuebingen, 72076, Germany
   Michael Weller & Johannes Dichgans

Authors

1. Brigit Brenner
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2. Klaus Ferlinz
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3. Heike Grassmé
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4. Michael Weller
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5. Ursula Koppenhoefer
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6. Johannes Dichgans
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7. Konrad Sandhoff
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8. Florian Lang
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9. Erich Gulbins
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Edited by D. Green

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Brenner, B., Ferlinz, K., Grassmé, H. et al. Fas/CD95/Apo-I activates the acidic sphingomyelinase via Caspases.Cell Death Differ 5, 29–37 (1998). https://doi.org/10.1038/sj.cdd.4400307

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• Received: 06 May 1997
• Revised: 27 June 1997
• Accepted: 30 July 1997
• Published: 28 January 1998
• Issue Date: 01 January 1998
• DOI: https://doi.org/10.1038/sj.cdd.4400307

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