title: Keratinocyte ATP binding cassette transporter expression is regulated by ultraviolet light.
abstract: 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.
authors.affiliation: Institute for Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany.
authors.forename: Lóránt
authors.initials: L
authors.lastname: Markó
authors.forename: György
authors.initials: G
authors.lastname: Paragh
authors.forename: Péter
authors.initials: P
authors.lastname: Ugocsai
authors.forename: Alfred
authors.initials: A
authors.lastname: Boettcher
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
authors.forename: Petra
authors.initials: P
authors.lastname: Schling
authors.forename: Attila
authors.initials: A
authors.lastname: Balogh
authors.forename: Victoria
authors.initials: V
authors.lastname: Tarabin
authors.forename: Evelyn
authors.initials: E
authors.lastname: Orsó
authors.forename: Norbert
authors.initials: N
authors.lastname: Wikonkál
authors.forename: József
authors.initials: J
authors.lastname: Mandl
authors.forename: Eva
authors.initials: E
authors.lastname: Remenyik
authors.forename: Gerd
authors.initials: G
authors.lastname: Schmitz
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D001692:Biological Transport; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D000078404:Epidermal Cells; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects*; D050356:Lipid Metabolism / Q000187:drug effects / Q000528:radiation effects; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000494:pharmacology; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D018528:ATP-Binding Cassette Transporters; D012333:RNA, Messenger; D011837:Radiation-Protective Agents