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

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. I...

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Veröffentlicht in:Experimental dermatology 2018-05, Vol.27 (5), p.473-475
Hauptverfasser: Smith, Sarah A., Colley, Helen E., Sharma, Parveen, Slowik, Klaudia M., Sison‐Young, Rowena, Sneddon, Andrew, Webb, Steven D., Murdoch, Craig
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Sprache:eng
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Zusammenfassung: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.
ISSN:0906-6705
1600-0625
DOI:10.1111/exd.13483