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

Abstract

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 (TESE), 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.

Metadata

Authors/Creators:

Smith, S.A.
Colley, H.E.
Sharma, P.
Slowik, K.M.
Sison-Young, R.
Sneddon, A.
Webb, S.D.
Murdoch, C. https://orcid.org/0000-0001-9724-122X

This is the peer reviewed version of the following article: Smith, S. A., Colley, H. E., Sharma, P., Slowik, K. M., Sison-Young, R., Sneddon, A., Webb, S. D. and Murdoch, C. (2017), Expression and enzyme activity of Cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue engineered skin equivalents. Exp Dermatol., which has been published in final form at https://doi.org/10.1111/exd.13483. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.

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