Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents.

Autor: Smith SA; School of Clinical Dentistry, University of Sheffield, Sheffield, UK., Colley HE; School of Clinical Dentistry, University of Sheffield, Sheffield, UK., Sharma P; MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK., Slowik KM; School of Clinical Dentistry, University of Sheffield, Sheffield, UK., Sison-Young R; MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK., Sneddon A; Department of Applied Mathematics, Liverpool John Moores University, Liverpool, UK., Webb SD; Department of Applied Mathematics, Liverpool John Moores University, Liverpool, UK., Murdoch C; School of Clinical Dentistry, University of Sheffield, Sheffield, UK.
Jazyk: angličtina
Zdroj: Experimental dermatology [Exp Dermatol] 2018 May; Vol. 27 (5), pp. 473-475. Date of Electronic Publication: 2018 Jan 05.
DOI: 10.1111/exd.13483
Abstrakt: CYP3A4 and CYP4A5 share specificity for a wide range of xenobiotics with the CYP3 subfamily collectively involved in the biotransformation of approximately 30% of all drugs. CYP3A4/5 mRNA transcripts have been reported in the skin, yet knowledge of their protein expression and function is lacking. In this study, we observed gene and protein expression of CYP3A4/5 in both human skin and tissue-engineered skin equivalents (TESEs), and enzyme activity was detected using the model substrate benzyl-O-methyl-cyanocoumarin. Mass spectrometric analysis of TESE lysates following testosterone application revealed a time-dependent increase in metabolite production, confirming the functional expression of these enzymes in skin.
(© 2017 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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