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Expression and enzyme activity of cytochrome P450 enzymes CYP 3A4 and CYP 3A5 in human skin and tissue‐engineered skin equivalents
Author(s) -
Smith Sarah A.,
Colley Helen E.,
Sharma Parveen,
Slowik Klaudia M.,
SisonYoung Rowena,
Sneddon Andrew,
Webb Steven D.,
Murdoch Craig
Publication year - 2018
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/exd.13483
Subject(s) - cyp3a4 , cytochrome p450 , enzyme , xenobiotic , human skin , cyp1b1 , biochemistry , metabolite , biotransformation , subfamily , chemistry , gene expression , biology , gene , genetics
CYP 3A4 and CYP 4A5 share specificity for a wide range of xenobiotics with the CYP 3 subfamily collectively involved in the biotransformation of approximately 30% of all drugs. CYP 3A4/5 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 CYP 3A4/5 in both human skin and tissue‐engineered skin equivalents ( TESE s), 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.