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DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way

Oncogene volume 21, pages 5844–5851 (2002)Cite this article

Abstract

Nuclear DNA damage and death receptor (CD95) activation by ultraviolet-B radiation (UVB) play a major role in UVB-induced apoptosis. Removal of DNA damage combined with inhibition of death receptor activation resulted in pronounced but not complete suppression of apoptosis, indicating that a third independent pathway is involved. Since reactive oxygen species (ROS) cause apoptosis and are induced by UVB, the radical scavenger pyrrolidene-dithiocarbamate (PDTC) was used. PDTC prevented UVB-induced apoptosis partially, H2O2-induced cell death largely, but not CD95-mediated apoptosis. The same was observed for cytochrome c release from mitochondria, another important event during apoptosis. The proapoptotic protein Bid was cleaved upon exposure to UVB or to agonistic anti-CD95-antibodies, but not to H2O2, indicating that H2O2 uses a different pathway. The fact that PDTC neither inhibited CD95-mediated apoptosis nor affected UV-induced DNA damage indicated that ROS generated during UVB irradiation may directly trigger mitochondrial cytochrome c release, thereby contributing to apoptosis. Accordingly, complete inhibition of apoptosis was observed when in addition to DNA damage removal via photoreactivation and blockade of CD95 signaling by caspase-8 inhibitor zIETD, PDTC was added before UVB exposure. This indicates that DNA damage, death receptor activation and ROS formation contribute to UVB-induced apoptosis in an essential and independent way.

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Abbreviations

BHA:

butylated hydroxyanisole

CPD:

cyclobutane pyrimidine dimers

NAC:

N-acetyl-cysteine

PDTC:

pyrrolidene-dithiocarbamate

ROS:

reactive oxygen species

UV:

ultraviolet radiation

UVB:

ultraviolet-B radiation

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Acknowledgements

The authors are grateful to D Yarosh, AGI-Dermatics for generous supply of Photosomes®. This work was supported by grants from the Federal Ministery of Education and Research (07UVB63A/5), the European Community (ENV4-CT97-0556) and the Interdisciplinary Center for Clinical Research (1ZKF, E10).

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Authors and Affiliations

  1. Department of Dermatology, Ludwig Boltzmann Institute for Cell Biology and Immunobiology of the Skin, University Münster, Münster, D-48149, Germany

    Dagmar Kulms, Elke Zeise, Birgit Pöppelmann & Thomas Schwarz

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  1. Dagmar Kulms
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  4. Thomas Schwarz
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Correspondence to Thomas Schwarz.

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Kulms, D., Zeise, E., Pöppelmann, B. et al. DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogene 21, 5844–5851 (2002). https://doi.org/10.1038/sj.onc.1205743

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