Expression of P450 enzymes in rat whole skin and cultured epidermal keratinocytes.
The complement and level of expression of P450 enzymes in male Fischer F344 rat whole skin and cultured keratinocytes were investigated using a panel of mono-specific antibodies. In whole skin microsomal fraction, immunoreactive bands corresponding to CYP2B12, CYP2C13, CYP2D1, CYP2D4, CYP2E1, CYP3A1, and CYP3A2 were detected whereas CYP1A1, CYP1A2, and CYP2C12 were absent. Skin levels were all between 0.1% and 4.7% of those found in liver, except for CYP2D4, which was not detected in liver. Keratinocytes were isolated from rat skin, cultured for up to 42 days, and changes in the levels of CYP3A1, CYP3A2, and CYP2E1 determined. Levels were low in isolated keratinocytes, but they increased markedly in culture, reaching a maximum at 10-14 days, where they were similar to those found in fresh skin. This suggests that primary keratinocytes grown in culture for 10-14 days may provide a useful experimental model to study P450-catalysed metabolism of xenobiotics in skin.
Zhu
Zheying
Z
Molecular Toxicology, Division of Biomedical Sciences, Faculty of Medicine, Imperial College, South Kensington, London SW7 2AZ, UK.
Hotchkiss
Sharon A
SA
Boobis
Alan R
AR
Edwards
Robert J
RJ
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D019392:Cytochrome P-450 CYP2E1 / Q000096:biosynthesis; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000235:genetics; D020869:Gene Expression Profiling; D015603:Keratinocytes / Q000201:enzymology* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D051381:Rats; D012867:Skin / Q000201:enzymology* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000096:biosynthesis
D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; C465138:Cyp3a23-3a1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; C022657:steroid hormone 6-beta-hydroxylase