Characterization of distinct forms of cytochromes P-450, epoxide metabolizing enzymes and UDP-glucuronosyltransferases in rat skin

Pham, Mai Anh; Magdalou, Jacques; Totis, Muriel; Fournel-Glgleux, Sylvie; Siest, Gérard; Hammock, Bruce D.

doi:10.1016/0006-2952(89)90075-0

Cited by 41 publications

(20 citation statements)

References 26 publications

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“…This suggested that in EPXH2, the Sp1 site immediately upstream of the putative transcriptional start site is essential for expression. Because Sp1 expression is generally ubiquitous [64] such a promoter system could explain the ubiquitous expression of sEH in numerous tissues in mammals [17,20,21,23,[25][26][27][28][29][30][65][66][67]. However, it does not explain the regulation of EPHX2 by PPAR-alpha agonists and testosterone as predicted from in vivo induction studies in rodents.…”

Section: Discussionmentioning

confidence: 99%

“…sEH activity is highest in mammalian liver and kidney [20][21][22][23], but it has also been found in many other tissues. In humans and rodents sEH expression occurs in liver, kidney, lung, heart, gut, brain, placenta, bladder, prostate, testis, spleen, skin, ovary, vascular endothelium, and some smooth muscle [13,17,[24][25][26][27][28][29][30][31][32]. Although the distribution and tissue-enriched expression of sEH have been studied, the molecular mechanisms of sEH regulation are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Transcriptional regulation of the human soluble epoxide hydrolase gene EPHX2

Tanaka

Kamita

Wolf

et al. 2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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Soluble epoxide hydrolase (sEH) is a multifunctional protein encoded by the EPHX2 gene. The biological functions and enzyme kinetics of sEH have been extensively investigated, however, little is known about its transcriptional regulation and mechanisms of tissue specific expression. Here, a luciferase gene based reporter assay was used to identify the minimal promoter and cis regulatory elements of EPHX2. The minimal promoter was identified as a GC-rich region between nts −374 to +28 with respect to the putative transcriptional start site. A reporter plasmid carrying this minimal promoter showed higher or similar activities in comparison to a reporter plasmid carrying nts −5,974 to +28 of EPHX2 in 9 human cell lines that were tested. Sp1 binding sites that are involved in augmenting the minimal promoter activity of EPHX2 were identified by nested deletion analysis, site-specific mutation, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Transcriptional regulation of the human soluble epoxide hydrolase gene EPHX2

Tanaka

Kamita

Wolf

et al. 2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

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“…The expression and modulation of CYP1A1 is associated with the AHH activ ity in the skin [20][21][22], which is responsible for the metabolic activation of PAHs such as BaP. The 7-ethoxycoumarin deethylase (ECOD) and the EROD activities are also cat alyzed by CYP1A1 in the skin.…”

Section: Ah H Activity In Skinmentioning

confidence: 99%

Cytochrome P-450 and Drug Development for Skin Diseases

Ahmad

Agarwal²,

Mukhtar³

1996

Skin Pharmacol Physiol

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Cytochromes P-450 (CYPs) are the most versatile and important class of drug-metabolizing enzymes which are induced in mammalian skin in response to xenobiotic exposure. CYPs are the target of special interest in the development of pharmaceuticals for skin diseases because most, if not all, drugs available in the armamentarium of the dermatologist are substrates, inducers or inhibitors of this enzyme family. The functional significance of drug metabolism in the skin and the implication of CYP in skin pathology and therapy is an area for future investigation. A detailed insight into the mechanism of action of various cutaneous CYPs, being capable of modulating the drug bioavailability, will be helpful in the development of better strategies for novel therapy against constantly increasing skin disorders. This brief review puts some of these perspectives together and suggests additional research in the area of CYPs with regard to their expression and modulation in mammalian skin as well as their implication in dermatological disorders and the therapy of skin diseases.

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“…Although constitutive expression of xenobiotic-metabolizing enzymes has been detected in normal keratinocytes [2,3] the levels of drug-metabolizing enzymes are generally much lower in the skin than those in the liver and intestine [4][5][6][7]. Thus, skin permeability rather than drug metabolism appears to be the major barrier to topical bioavailability [8,9].…”

Section: Introductionmentioning

confidence: 99%

Characterization of SLC transporters in human skin

Alriquet¹,

Sevin²,

Gaborit³

et al. 2015

ADMET DMPK

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Most identified drug transporters belong to the ATP-binding Cassette (ABC) and Solute Carrier (SLC) families. Recent research indicates that some of these transporters play an important role in the absorption, distribution and excretion of drugs, and are involved in clinically relevant drug-drug interactions for systemic drugs. However, very little is known about the role of drug transporters in human skin in the disposition of topically applied drugs and their involvement in drug-drug interactions. The aim of this work was to compare the expression in human skin (vs human hepatocytes and kidney) of SLC transporters included in the EMA guidance as the most likely clinical sources of drug interactions. The expression of SLC transporters in human tissues was analyzed by quantitative RT-PCR. Modulation of SLC47A1 and SLC47A2 (MATE1 and MATE2) expression was analyzed after treatment of human skin in organ-culture with rifampicin and UV irradiation. The expression of SLCO2B1 (OATPB), SLCO3A1 (OATPD), SLCO4A1 (OATPE), SLC47A1 and SLC47A2 (MATE1 and MATE2)

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Characterization of distinct forms of cytochromes P-450, epoxide metabolizing enzymes and UDP-glucuronosyltransferases in rat skin

Cited by 41 publications

References 26 publications

Transcriptional regulation of the human soluble epoxide hydrolase gene EPHX2

Transcriptional regulation of the human soluble epoxide hydrolase gene EPHX2

Cytochrome P-450 and Drug Development for Skin Diseases

Characterization of SLC transporters in human skin

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