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The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells

Oncogene volume 20, pages 6493–6502 (2001)Cite this article

Abstract

The activation of sphingomyelinases leading to the generation of ceramide has been implicated in various apoptotic pathways. However, the role of ceramide as an essential death mediator remains highly controversial. In the present study, we investigated the functional relevance of ceramide in a genetic model by using primary cells from a Farber disease patient. These cells accumulate ceramide as the result of an inherited deficiency of acidic ceramidase. We demonstrate that Farber disease lymphocytes and fibroblasts underwent apoptosis induced by various stress stimuli, including staurosporine, anticancer drugs and γ-irradiation, equally as normal control cells. In addition, caspase activation by these proapoptotic agents occurred rather similarly in Farber disease and control fibroblasts. Interestingly, Farber disease lymphoid cells underwent apoptosis induced by the CD95 death receptor more rapidly than control cells. Our data therefore suggest that ceramide does not play an essential role as a second messenger in stress-induced apoptosis. However, in accordance with a role in lipid-rich microdomains, ceramide by altering membrane composition may function as an amplifier in CD95-mediated apoptosis.

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Acknowledgements

This work was supported by grants from the Interdisciplinary Center of Clinical Research (IZKF) of the University of Münster, the Deutsche Krebshilfe, the Deutsche Forschungsgemeinschaft (SFB 293) and the German Federal Ministry of Education and Research with the German-Israeli Project Cooperation (DIP).

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  1. Marek Los and Klaus Schulze-Osthoff: M Los and K Schulze-Osthoff have contributed equally to this work

Authors and Affiliations

  1. Department of Immunology and Cell Biology, University of Münster, Münster, Germany

    Christof Burek, Marek Los & Klaus Schulze-Osthoff

  2. Department of Pediatrics, University of Münster, Münster, Germany

    Johannes Roth & Hans-Georg Koch

  3. Neurochemical Laboratory, University of Tübingen, Tübingen, Germany

    Klaus Harzer

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  1. Christof Burek
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Correspondence to Klaus Schulze-Osthoff.

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Burek, C., Roth, J., Koch, HG. et al. The role of ceramide in receptor- and stress-induced apoptosis studied in acidic ceramidase-deficient Farber disease cells. Oncogene 20, 6493–6502 (2001). https://doi.org/10.1038/sj.onc.1204841

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