The goal of this research program is to develop a better understanding about how vitamin D3 is made and processed in the skin. During the past four years, we have accomplished the major Specific Aims that we had proposed in our last grant period and established a very sensitive high performance liquid chromatography methodology that will be important for continuing studies on the photobiology of previtamin D and vitamin D3. Ten photoproducts of previtamin D3 and six photoproducts of vitamin D3 have now been identified after exposure to ultraviolet radiation that is comparable to human exposure levels. We plan to study the photoproduction of toxisterols and suprasterols in a liposomal model and human skin equivalent, and in cultured human keratinocytes and human skin. The biologic activity of the various toxisterols and suprasterols will be investigated in cultured human keratinocytes with specific emphasis on regulation of cellular proliferation and terminal differentiation. In addition, we will evaluate the metabolism of the most prominent toxisterols and sprasterols that are produced in the skin. This will be accomplished by making tritium-labeled toxisterols and sprasterols, and evaluating their metabolism in cultured human keratinocytes. Results from this study should provide important new insights into the photoproduction of toxisterols and suprasterols in human skin and provide new information about their potential biologic functions in the skin.
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