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Ceramide does not act as a general second messenger for ultraviolet-induced apoptosis
Jiong Deng1, Haifan Zhang, Freke Kloosterboer
1Department of Molecular and Cellular Oncology, Box 108, The University of Texas, MD Anderson Cancer Center, Houston, Texas, TX 77030, USA.
Oncogene
|January 16, 2002
Summary
Ceramide is not a general second messenger for ultraviolet (UV)-induced apoptosis. Studies show UV-induced cell death pathways differ from ceramide-induced apoptosis, challenging its proposed role.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Ceramide is implicated as a second messenger in stress-induced apoptosis.
- Understanding the precise role of ceramide in UV-induced apoptosis is crucial.
Purpose of the Study:
- To investigate the role of ceramide as a second messenger in ultraviolet (UV)-induced apoptosis.
- To differentiate the molecular pathways of UV-induced and ceramide-induced apoptosis.
Main Methods:
- Characterization of murine melanoma cells and their E1A transfectants.
- Assessment of cellular sensitivity to UV radiation and exogenous ceramide.
- Evaluation of endogenous ceramide elevation following UV exposure.
- Inhibition studies using interleukin-1beta-converting enzyme (ICE) inhibitor z-VAD.
Main Results:
- E1A transfectants showed increased UV-induced apoptosis sensitivity but lower relative ceramide elevation compared to parental cells.
- UV-resistant melanoma cells were more sensitive to exogenous ceramide than UV-sensitive E1A transfectants.
- Persistent ceramide exposure, not transient, was required for apoptosis, unlike UV action.
- UV-induced apoptosis was inhibited by z-VAD, while ceramide-induced apoptosis was not.
Conclusions:
- Ceramide does not function as a general second messenger for UV-induced apoptosis.
- UV-induced and ceramide-induced apoptosis involve distinct molecular pathways.
- The findings challenge the established model of ceramide's role in UV-mediated cell death.