C. Popa et al., Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid-inducible, BR J DERM, 141(3), 1999, pp. 460-468
Retinoids, and their synthetic analogues, are well-established regulators o
f the squamous differentiation programme both in vivo and in vitro. Despite
this, very few studies have focused on the mechanism by which retinoid act
ion is terminated, e.g. metabolism, Recently, a new cytochrome P450 family
member (CYP26AI) was cloned. CUP26AI was reported to have substrate specifi
city for retinoids and to be retinoid-inducible. In this study, we have exa
mined the expression and retinoic acid (RA) inducibility of CYP26AI in huma
n 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 tr
ansglutaminase was still repressed by RA in the same cultures. Despite the
lo iv levels of CYP26AI expression in the keratinocytes, the keratinocytes
were still capable of significant RA metabolism, In conclusion, our study r
eports, for the first time, that CYP26AI is unlikely to contribute to RA me
tabolism in keratinocytes. These studies also indicate that. as pet unknown
isoforms of cytochrome P450 may be involved in RA metabolism in keratinocy
tes.