Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue‐engineered skin equivalents. Issue 5 (5th January 2018)

• Record Type: Journal Article
• Authors: Smith, Sarah A.; Colley, Helen E.; Sharma, Parveen; Slowik, Klaudia M.; Sison‐Young, Rowena; Sneddon, Andrew; Webb, Steven D.; Murdoch, Craig
• Other Names: Schneider Marlon R. guestEditor.; Pincelli Carlo guestEditor.
• Is Part Of: Experimental dermatology. Volume 27:Issue 5(2018)
• Page Start: 473
• Page End: 475
• Publication Date: 2018-01-05
• Subjects: epithelium -- steroids -- three‐dimensional tissue models -- toxicity -- xenobiotic metabolism; Dermatology -- Periodicals; 616.5
• DOI: 10.1111/exd.13483
• Languages: English
• ISSNs: 0906-6705

Abstract

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 (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.