UVA/B exposure promotes the biosynthesis of dehydroretinol in cultured human keratinocytes.
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.
Living Skin Bank, Department of Oral Biology and Pathology, School of Dental Medicine, Stony Brook University, Stony Brook, NY 11794-8702, USA. juliana.tafrova@sbumed.org
Juliana I
JI
Tafrova
Adriana
A
Pinkas-Sarafova
Erik
E
Stolarzewicz
Kathlyn A
KA
Parker
Marcia
M
Simon
D000217:Acyltransferases / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D004072:Digitonin / Q000494:pharmacology; D004789:Enzyme Activation / Q000528:radiation effects*; D004952:Esters / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000378:metabolism* / Q000528:radiation effects; D014466:Ultraviolet Rays; D014801:Vitamin A / Q000031:analogs & derivatives* / Q000096:biosynthesis* / Q000378:metabolism*
D004952:Esters; D053222:Fas Ligand Protein; D011837:Radiation-Protective Agents; C024366:vitamin A2; D014801:Vitamin A; D000217:Acyltransferases; D004072:Digitonin