Keratinocyte ATP binding cassette transporter expression is regulated by ultraviolet light

• Published in: Journal of photochemistry and photobiology. B, Biology Vol. 116; pp. 79 - 88
• Main Authors: Markó, Lóránt, Paragh, György, Ugocsai, Péter, Boettcher, Alfred, Vogt, Thomas, Schling, Petra, Balogh, Attila, Tarabin, Victoria, Orsó, Evelyn, Wikonkál, Norbert, Mandl, József, Remenyik, Éva, Schmitz, Gerd
• Format: Journal Article
• Language: English
• Published: Switzerland Elsevier B.V 05.11.2012
• Subjects: ABC transporter; ABC transporters; alternative splicing; ATP-Binding Cassette Transporters - genetics; biogenesis; Biological Transport; Cell Differentiation - drug effects; Cell Differentiation - radiation effects; cholesterol; Down-Regulation - drug effects; Down-Regulation - radiation effects; Epidermal barrier; Epidermis - cytology; Epidermis - drug effects; Epidermis - metabolism; Epidermis - radiation effects; Gene Expression Regulation - drug effects; Gene Expression Regulation - radiation effects; homeostasis; Humans; ichthyosis; irradiation; Keratinocyte; keratinocytes; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Keratinocytes - radiation effects; keratinosomes; Lipid Metabolism - drug effects; Lipid Metabolism - radiation effects; Lipid transport; luciferase; messenger RNA; photobiology; photochemistry; Promoter Regions, Genetic - drug effects; Promoter Regions, Genetic - genetics; Promoter Regions, Genetic - radiation effects; Radiation-Protective Agents - pharmacology; RNA, Messenger - genetics; RNA, Messenger - metabolism; sulfates; ultraviolet radiation; Ultraviolet Rays - adverse effects; UVB; UVB; Keratinocyte; Epidermal barrier; ABC transporter; Lipid transport
• ISSN: 1011-1344; 1873-2682
• DOI: 10.1016/j.jphotobiol.2012.06.007

Many ATP binding cassette (ABC) transporters are important regulators of lipid homeostasis and have been implicated in keratinocyte lipid transport. Ultraviolet (UV) light exposure is a known epidermal stressor, which amongst other effects causes lipid alterations and defective lamellar body biogenesis. To elucidate the background of these lipid changes we studied the effect of UVB light on ABC transporter expression. The effect of UVB treatment on the levels of 47 known human ABC transporter mRNAs was analyzed in normal human epidermal keratinocytes. Immunoblots and promoter assays were carried out for ABCA1 and ABCG1. The mRNA levels of cholesterol transport regulators ABCA1 and ABCG1 were markedly downregulated by UVB, parallel to the lamellar ichthyosis related glucosylceramide transporter ABCA12 and the suspected sphingosine-1-phosphate and cholesterol sulfate transporter ABCC1. The long but not the short alternative splice variant of the ABCF2 was found to be markedly upregulated rapidly after UVB irradiation. Immunoblot confirmed ABCA1 and ABCG1 protein downregulation, and luciferase assays showed suppression of their promoters by UVB. These proteins mostly transport lipids, which account for the integrity of the epidermal barrier; therefore our findings on the UVB regulation of ABC transporters may explain the appearance of barrier dysfunction after UVB exposure.