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Ceramide does not act as a general second messenger for ultraviolet-induced apoptosis

Oncogene volume 21, pages 44–52 (2002)Cite this article

Abstract

Ceramide has been proposed as a second messenger for stress-induced apoptosis. By characterization of murine melanoma cells and their E1A transfectants, we found several lines of evidences against the role of ceramide as a second messenger for ultraviolet (UV)-induced apoptosis. First, although E1A transfected melanoma cells were more sensitive to UV-induced apoptosis than parental cells, the relative endogenous ceramide elevation induced by UV was greater in parental cells than in E1A transfectants. Second, UV-resistant melanoma cells were more sensitive to exogenous ceramide than UV-sensitive E1A transfectants. The differential responses to UV and ceramide by E1A require the same functional CR2 domain of E1A. Third, unlike the action of UV, transient exposure (up to 2 h) of lethal dose of ceramide was not sufficient to cause apoptosis in these cells, and persistent presence of ceramide was required for processing the apoptotic process. Finally, ceramide and UV do not share a common pathway in apoptosis induction. UV-induced apoptosis was blocked by interleukin-1β-converting enzyme (ICE) inhibitor z-VAD whereas ceramide-induced apoptosis was not. Therefore, we conclude that ceramide is not a general second messenger for UV-induced apoptosis.

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Acknowledgements

We thank Dr Stanley T Bayley for providing the mutant E1A plasmid constructs. This research was supported by grants R01 CA58880, CA77858, and cancer center core grant 16672 from the National Cancer Institute; MD Anderson Faculty Achievement Award; and the Breast Cancer Research Program.

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Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, Box 108, The University of Texas, MD Anderson Cancer Center, Houston, 77030, Texas, TX, USA

    Jiong Deng, Freke Kloosterboer, Yong Liao, Jim Klostergaard & Mien-Chie Hung

  2. The Lung Cancer Program, Allegheny University of the Health Sciences-Allegheny Campus, Pittsburgh, 15212, Pennsylvania, PA, USA

    Haifan Zhang & Mark L Levitt

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  1. Jiong Deng
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Correspondence to Mien-Chie Hung.

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Deng, J., Zhang, H., Kloosterboer, F. et al. Ceramide does not act as a general second messenger for ultraviolet-induced apoptosis. Oncogene 21, 44–52 (2002). https://doi.org/10.1038/sj.onc.1204900

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