title: Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid-inducible.
abstract: Retinoids, and their synthetic analogues, are well-established regulators of the squamous differentiation programme both in vivo and in vitro. Despite this, very few studies have focused on the mechanism by which retinoid action is terminated, e.g. metabolism. Recently, a new cytochrome P450 family member (CYP26AI) was cloned. CYP26AI was reported to have substrate specificity for retinoids and to be retinoid-inducible. In this study, we have examined the expression and retinoic acid (RA) inducibility of CYP26AI in human epidermis and cultured keratinocytes. We found very low levels of CYP26AI mRNA expression in both epidermis and keratinocytes. Furthermore, we found no evidence for RA inducibility of CYP26 mRNA expression. This lack of RA inducibility was not due to inactivity of the retinoids, as we show that transglutaminase was still repressed by RA in the same cultures. Despite the low levels of CYP26AI expression in the keratinocytes, the keratinocytes were still capable of significant RA metabolism. In conclusion, our study reports, for the first time, that CYP26AI is unlikely to contribute to RA metabolism in keratinocytes. These studies also indicate that as yet unknown isoforms of cytochrome P450 may be involved in RA metabolism in keratinocytes.
authors.affiliation: Epithelial Pathobiology Group, Centre for Immunology and Cancer Research, University of Queensland Department of Medicine, Princess Alexandra Hospital, Brisbane, Queensland 4102, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Popa
authors.forename: A J
authors.initials: AJ
authors.lastname: Dicker
authors.forename: A L
authors.initials: AL
authors.lastname: Dahler
authors.forename: N A
authors.initials: NA
authors.lastname: Saunders
mesh_terms: D002460:Cell Line / Q000201:enzymology; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004790:Enzyme Induction; D004817:Epidermis / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000201:enzymology* / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008297:Male; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis*; D000072516:Retinoic Acid 4-Hydroxylase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D012333:RNA, Messenger; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000072516:Retinoic Acid 4-Hydroxylase