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Photolytically generated nitric oxide inhibits caspase activity and results in AIF-mediated cell death

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Abstract

In human skin tissue nitrite is found at relatively high concentrations and represents the main source for cutaneous non-enzymatic nitric oxide (NO) formation during UVA exposure due to photolytical decomposition. Since NO has been repeatedly shown to act pro- as well as anti-apoptotic we here studied the effects of UVA irradiation on human keratinocytes in the presence of nitrite. We show that UVA-induced nitrite photodecomposition effectively inactivated caspase activity. In parallel, we observed in human skin keratinocytes, UVA-irradiated in the presence of nitrite, a proteolytic processing of apoptosis-inducing factor (AIF) followed by translocation from the mitochondrion into the nucleus. This translocation resulted in a characteristic apoptotic nuclear phenotype, which differs from the known nuclear phenotype of caspase-mediated chromatin condensation and apoptotic body formation. Interestingly both, AIF translocation and AIF-induced nuclear phenotype changes can be inhibited by NO scavengers, demonstrating the distinct role of nitrite-derived NO in the observed processes. This mode of UVA-induced apoptosis is AIF-dependent and NO-mediated and strongly depends on the presence of nitrite, abundantly present in skin tissue. Thus, photolysis of nitrite in the skin appears to represent an important backup mechanism, which ensures removal of UVA-damaged cells even in the absence of caspase activation.

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Acknowledgements

Active caspase-3 was kindly provided by Prof. Dr. K. Schultze-Osthoff. This work was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG), SFB 503, project A3.

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The authors state no conflict of interest.

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Authors and Affiliations

  1. Institute of Molecular Medicine, Research Group Immunobiology, Heinrich-Heine-University Duesseldorf, Universitaetsstraße 1, 40225, Duesseldorf, Germany

    Joerg Liebmann & Victoria Kolb-Bachofen

  2. Institute for Pathology, Heinrich-Heine-University Duesseldorf, Duesseldorf, Germany

    Csaba Mahotka

  3. Department of Plastic and Reconstructive Surgery, Hand Surgery, and Burn Center, Medical Faculty, RWTH Aachen University, Pauwelsstraße 30, 52057, Aachen, Germany

    Christoph V. Suschek

Authors
  1. Joerg Liebmann
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  2. Victoria Kolb-Bachofen
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  3. Csaba Mahotka
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  4. Christoph V. Suschek
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Correspondence to Joerg Liebmann.

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Liebmann, J., Kolb-Bachofen, V., Mahotka, C. et al. Photolytically generated nitric oxide inhibits caspase activity and results in AIF-mediated cell death. J Mol Med 88, 279–287 (2010). https://doi.org/10.1007/s00109-009-0551-3

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  • DOI: https://doi.org/10.1007/s00109-009-0551-3

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