Quantitation of cytochrome P450 mRNA levels in human skin

Yengi, Lilian G.; Xiang, Qian; Pan, Jingshun; Scatina, JoAnn; Kao, John Y.; Ball, S.; Fruncillo, Richard J.; Ferron, Géraldine M.; Wolf, Charles

doi:10.1016/s0003-2697(03)00042-3

Cited by 82 publications

(58 citation statements)

References 30 publications

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“…Although CYP2A6 mRNA was not detected in KCs, these same investigators observed message in fibroblasts and melanocytes (Saeki et al, 2002). Studies to date provide evidence for the expression of CYP2B6 mRNA in skin biopsy samples and KCs, with the latter also demonstrating the presence of CYP2B6 protein (Baron et al, 2001;Yengi et al, 2003).…”

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 92%

“…In contrast, studies probing for CYP1A2 mRNA have found that message for expression of this gene in skin or skin cells is undetectable (Baron et al, 2001;Saeki et al, 2002). CYP1B1 mRNA has been readily detected in skin biopsy samples and all skin cells examined to date (Baron et al, 2001;Saeki et al, 2002;Smith et al, 2003;Yengi et al, 2003).…”

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 95%

“…Early studies demonstrating the ability of animal skin to metabolize benzo[a]pyrene suggested expression of CYP1A1 in skin. Indeed, CYP1A1 mRNA has been found in all human skin sources probed to date, although data supporting expression of CYP1A1 protein is limited to KCs (Baron et al, 2001;Saeki et al, 2002;Yengi et al, 2003). In contrast, studies probing for CYP1A2 mRNA have found that message for expression of this gene in skin or skin cells is undetectable (Baron et al, 2001;Saeki et al, 2002).…”

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 99%

“…Although CYP2C9 mRNA was demonstrated in skin biopsy samples, message was not detectable in KCs or HaCaT cells, an immortalized keratinocyte cell line (Yengi et al, 2003;Vyas et al, 2006a). Assessment of the expression of CYP2C9 protein in KCs and HaCaT cells by immunoblot were inconclusive (Vyas et al, 2006a).…”

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 99%

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Biotransformation of Drugs in Human Skin

Svensson

2008

Drug Metab Dispos

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ABSTRACT:Although it is the largest organ of the human body, skin is often not considered in discussions of drug metabolism. However, there is growing evidence that most common drug-metabolizing enzymes are expressed in the skin. Evidence for expression of cytochromes P450, flavin monooxygenases, glutathione-S-transferases, N-acetyltransferases, and sulfotransferases in human skin and skin cells are presented. Additional discussion is focused on the evidence of actual metabolism of drugs. Finally, the potential clinical implications of metabolism within the skin are discussed briefly.Representing the largest organ in the human body, skin provides an important barrier role in protecting the body from external chemicals and pathogens that would otherwise impair critical functions needed for survival. Comprised of a complex cellular network, skin is capable of many metabolic functions common to visceral organs, including the biotransformation of drugs that penetrate through its most external layer. In addition to being an important target for pharmacotherapy, delivery through the skin is increasingly used as an effective means of delivering drugs to the systemic circulation. It is also evident that biotransformation within the skin may be an essential step to manifesting cutaneous toxicity to certain drugs and chemicals. Hence, an understanding of the capacity and impact of drug biotransformation within skin is an important component in assessing pharmacotherapy directed to or through the cutaneous environment. In the present article, discussion will be limited to evidence for biotransformation of drugs generated specifically in human skin or skin cells. Although many investigations have probed the ability of skin from numerous species to metabolize a variety of environmental chemicals, the focus of the present review is on evidence for metabolism of therapeutic agents. The reader is referred to the recent review of Oesch et al. (2007) for a comparison of xenobiotic-metabolizing enzymes in the skin of various species. Overview of the Structure and Function of SkinExisting as a dynamic and flexible barrier, human skin serves a multifaceted role as the organ with the greatest exposure to the external environment. In addition to providing the primary means for tactile evaluation of the immediate surroundings, skin serves a critical role in thermoregulation of the body. The plethora of infectious diseases with cutaneous manifestations attests to the important sentinel role of skin in protecting the body from bacterial, fungal, and viral pathogens. Although this diversity of function is recognized, it is not surprising that skin is populated by numerous types of specialized cells (see Table 1) that enable dynamic interaction with the internal and external environment. Because studies assessing the role of skin in drug metabolism often use model cells, it is important to begin this review with a brief discussion of skin structure and function.Three identifiable layers comprise human skin: epidermis, dermis, and hypodermi...

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Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 92%

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 95%

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 99%

Section: Evidence For the Expression Of Drug-metabolizing Enzymes In mentioning

confidence: 99%

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Biotransformation of Drugs in Human Skin

Svensson

2008

Drug Metab Dispos

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“…CYP2B6 is mainly expressed in liver, where it constitutes about 3-5% of the total microsomal P450 pool (Gervot et al, 1999;Lang et al, 2001), but it is also detected at lower levels in extrahepatic tissues, including intestine, kidney, lung, skin and the brain (Gervot et al, 1999;Miksys et al, 2003;Yengi et al, 2003). CYP2B6 activity in liver microsomes varies more than 100-fold and a broad inter-individual variability of in vivo pharmacokinetic parameters of several CYP2B6 drug substrates suggests significant interindividual differences in the systemic exposure to a variety of drugs that are metabolized by CYP2B6 (Ekins et al, 1998).…”

Section: Cyp2b6mentioning

confidence: 99%

Cytochrome P450 pharmacogenetics and cancer

2006

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The cytochromes P450 (CYPs) are key enzymes in cancer formation and cancer treatment. They mediate the metabolic activation of numerous precarcinogens and participate in the inactivation and activation of anticancer drugs. Since all CYPs that metabolize xenobiotics are polymorphic, much emphasis has been put on the investigation of a relationship between the distribution of specific variant CYP alleles and risk for different types of cancer, but a consistent view does not yet exist. This is to a great extent explained by the fact that the CYPs involved in activation of precarcinogens are in general not functionally polymorphic. This is in contrast to CYPs that are active in drug biotransformation where large interindividual differences in the capacity to metabolize therapeutic drugs are seen as a consequence of polymorphic alleles with altered function. This includes also some anticancer drugs like tamoxifen and cyclophosphamide metabolized by CYP2D6, CYP2C19 and CYP2B6. Some P450 forms are also selectively expressed in tumours, and this could provide a mechanism for drug resistance, but also future therapies using these enzymes as drug targets can be envisioned. This review gives an upto-date description of our current knowledge in these areas.

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Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes

Dolžan

2012

Pharmacogenetics and Individualized Therapy

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Quantitation of cytochrome P450 mRNA levels in human skin

Cited by 82 publications

References 30 publications

Biotransformation of Drugs in Human Skin

Biotransformation of Drugs in Human Skin

Cytochrome P450 pharmacogenetics and cancer

Pharmacogenetics in Drug Metabolism: Role of Phase I Enzymes

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