Expression pattern of human ATP-binding cassette transporters in skin.

Saya Takenaka,Ryoichi Fujiwara,Tomoo Itoh

doi:10.1002/prp2.5

Saya Takenaka, Ryoichi Fujiwara + Show 1 more

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https://doi.org/10.1002/prp2.5

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Journal: Pharmacology Research & Perspectives	Publication Date: Sep 8, 2013
Citations: 27	License type: CC BY 3.0

Affiliation: Kitasato University

Abstract

ATP-binding cassette (ABC) transporters transport a variety of substrates across cellular membranes coupled with hydrolysis of ATP. Currently 49 ABC transporters consisting of seven subfamilies, ABCA, ABCB, ABCC, ABCD, ABCE, ABCF, and ABCG, have been identified in humans and they are extensively expressed in various tissues. Skin can develop a number of drug-induced toxicities' such as Stevens–Johnson syndrome and psoriasis. Concentration of drugs in the skin cells is associated with the development of adverse drug reactions. ABC transporters play important roles in absorption and disposition of drugs in the cells; however, the expression pattern of human ABC transporters in the skin has not been determined. In this study, the expression patterns of 48 human ABC transporters were determined in the human skin as well as in the liver and small intestine. Most of the ABCA, ABCB, ABCC, ABCD, ABCE, and ABCF family members were highly or moderately expressed in the skin, while ABCG family members were slightly expressed in the skin. Significant interindividual variability was also observed in the expression levels of those ATP transporters in the skin, except for ABCA5 and ABCF1, which were found to be expressed in all of the human skin samples tested in this study. In conclusion, this is the first study to identify the expression pattern of the whole human ABC family of transporters in the skin. The interindividual variability in the expression levels of ABC transporters in the human skin might be associated with drug-induced skin diseases.

Highlights

Most of the ATP-binding cassette (ABC) transporter genes encode functional transmembrane proteins that utilize the energy of ATP hydrolysis to transport their substrates across membranes (Dean et al 2001a)
Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics
The skin is the primary tissue that protects our body from ultraviolet irradiation, infection, microorganisms, and exogenous toxic compounds, it is one of the tissues where severe adverse reactions caused by administered drugs, such as Stevens–Johnson syndrome (Fritsch and Sidoroff 2000), psoriasis (Tsankov et al 2000), allergy (Kaplan 1984), drug-induced hypersensitivity syndrome (Shiohara et al 2006), Lyell syndrome (Saiag et al 1992), and druginduced photosensitivity (Harber and Baer 1972) are seen

Summary

Introduction

Most of the ATP-binding cassette (ABC) transporter genes encode functional transmembrane proteins that utilize the energy of ATP hydrolysis to transport their substrates across membranes (Dean et al 2001a). ABC transporters transport a wide variety of endogenous compounds across extra- and intracellular membranes, including cholesterol, peptides, iron, ions, bile salts, and lipids (Borst et al 2000; Schmitz et al 2000, 2001; Lu et al 2001). They transport exogenous compounds such as clinically used drugs (Glavinas et al 2004). Certain subtypes of the ABC transporters, such as ABCB1 and ABCB4,

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