UVA/B exposure promotes the biosynthesis of dehydroretinol in cultured human keratinocytes
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Retinol and its metabolites modulate epithelial differentiation and serve as cellular UV sensors through changes in retinoid status. Of note is the dehydroretinol family which may serve functions distinct from parental retinol. This study focuses on the metabolism of this family and its potential participation in the response of normal epidermal human keratinocytes to UV irradiation. There were three findings. First, keratinocytes contain two pools of dehydroretinyl esters, one of which is shielded from UVB-, but not from UVA-induced decomposition. Second, using a novel in vitro assay we demonstrated that both UVA and UVB promote dehydroretinol biosynthesis in keratinocytes, but only UVB exposure promotes retinoid ester accretion by enhancing the activity of at least one acyl transferase. Finally, dehydroretinol sufficiency reduces UVA/B driven apoptosis more effectively than retinol sufficiency. This may in part be due to differences in the expression of Fas ligand, which we found to be upregulated by retinoic acid, but not dehydroretinoic acid. These observations implicate a role of dehydroretinol and its metabolites in UVA/B adaptation. Thus, the keratinocyte response to UV is jointly shaped by both the retinoids and dehydroretinoids.
KeywordsVitamin A2 Dehydroretinol 3,4-Didehydroretinoic acid Retinol UVA UVB
We thank Dr. Betsy Sutherland, Dr. John Sutherland, Dr. Stefan Tafrov, and John Trunk for giving us the opportunities to perform the UV irradiations experiments in their laboratories at Brookhaven National Laboratories. We especially appreciate their helpful advice, support and understanding. This research was funded in part by a grant to Prof. M. Simon from Unilever Research and Development, US. M. Simon is a consultant to Unilever Research and Development, US.
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