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

Sarah A Smith; Helen E Colley; Parveen Sharma; Klaudia M Slowik; Rowena Sison-Young; Andrew Sneddon; Steve Webb; Craig Murdoch

doi:10.1111/exd.13483

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

Sarah A Smith, Helen E Colley, Parveen Sharma, Klaudia M Slowik, Rowena Sison-Young, Andrew Sneddon, Steve Webb, Craig Murdoch

Bristol Medical School (THS)

Research output: Contribution to journal › Article (Academic Journal)

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.

Original language	English
Pages (from-to)	473-475
Number of pages	3
Journal	Experimental Dermatology
Volume	27
Issue number	5
DOIs	https://doi.org/10.1111/exd.13483
Publication status	Published - May 2018

Bibliographical note

Keywords

Cytochrome P-450 CYP3A/metabolism
Humans
Liver/enzymology
Models, Biological
Skin/enzymology
Tissue Engineering

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title = "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 (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.",

keywords = "Cytochrome P-450 CYP3A/metabolism, Humans, Liver/enzymology, Models, Biological, Skin/enzymology, Tissue Engineering",

author = "Smith, {Sarah A} and Colley, {Helen E} and Parveen Sharma and Slowik, {Klaudia M} and Rowena Sison-Young and Andrew Sneddon and Steve Webb and Craig Murdoch",

note = "{\textcopyright} 2017 The Authors. Experimental Dermatology Published by John Wiley & Sons Ltd.",

year = "2018",

month = may,

doi = "10.1111/exd.13483",

language = "English",

volume = "27",

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journal = "Experimental Dermatology",

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Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents. / Smith, Sarah A; Colley, Helen E; Sharma, Parveen; Slowik, Klaudia M; Sison-Young, Rowena; Sneddon, Andrew; Webb, Steve; Murdoch, Craig.

In: Experimental Dermatology, Vol. 27, No. 5, 05.2018, p. 473-475.

Research output: Contribution to journal › Article (Academic Journal)

TY - JOUR

T1 - Expression and enzyme activity of cytochrome P450 enzymes CYP3A4 and CYP3A5 in human skin and tissue-engineered skin equivalents

AU - Smith, Sarah A

AU - Colley, Helen E

AU - Sharma, Parveen

AU - Slowik, Klaudia M

AU - Sison-Young, Rowena

AU - Sneddon, Andrew

AU - Webb, Steve

AU - Murdoch, Craig

PY - 2018/5

Y1 - 2018/5

N2 - 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.

AB - 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.

KW - Cytochrome P-450 CYP3A/metabolism

KW - Humans

KW - Liver/enzymology

KW - Models, Biological

KW - Skin/enzymology

KW - Tissue Engineering

U2 - 10.1111/exd.13483

DO - 10.1111/exd.13483

M3 - Article (Academic Journal)

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VL - 27

SP - 473

EP - 475

JO - Experimental Dermatology

JF - Experimental Dermatology

SN - 0906-6705

IS - 5

ER -