Effects of UVB-induced oxidative stress on protein expression and specific protein oxidation in normal human epithelial keratinocytes: a proteomic approach

Marzia Perluigi1, Fabio Di Domenico1, Carla Blarzino1, Cesira Foppoli2, Chiara Cini1, Alessandra Giorgi1, Caterina Grillo1, Federico De Marco3, D. Allan Butterfield4, Maria Eugenia Schininà1, Raffaella Coccia1
1Department of Biochemical Sciences, "Sapienza" University of Rome - P.le A. Moro, 5 - 00185, Rome, Italy
2CNR Institute of Molecular Biology and Pathology - P.le A. Moro, 5 - 00185, Rome, Italy
3Laboratory of Virology, IFO - Regina Elena National Cancer Institute - V. Messi d'Oro, 156 - 00156, Rome, Italy
4Department of Chemistry, Center of Membrane Science, and Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, 40506, USA

Tóm tắt

Abstract Background

The UVB component of solar ultraviolet irradiation is one of the major risk factors for the development of skin cancer in humans. UVB exposure elicits an increased generation of reactive oxygen species (ROS), which are responsible for oxidative damage to proteins, DNA, RNA and lipids. In order to examine the biological impact of UVB irradiation on skin cells, we used a parallel proteomics approach to analyze the protein expression profile and to identify oxidatively modified proteins in normal human epithelial keratinocytes.

Results

The expression levels of fifteen proteins - involved in maintaining the cytoskeleton integrity, removal of damaged proteins and heat shock response - were differentially regulated in UVB-exposed cells, indicating that an appropriate response is developed in order to counteract/neutralize the toxic effects of UVB-raised ROS. On the other side, the redox proteomics approach revealed that seven proteins - involved in cellular adhesion, cell-cell interaction and protein folding - were selectively oxidized.

Conclusions

Despite a wide and well orchestrated cellular response, a relevant oxidation of specific proteins concomitantly occurs in UVB-irradiated human epithelial Keratinocytes. These modified (i.e. likely dysfunctional) proteins might result in cell homeostasis impairment and therefore eventually promote cellular degeneration, senescence or carcinogenesis.

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