title: Glutathione peroxidase-1 inhibits UVA-induced AP-2alpha expression in human keratinocytes.
abstract: In this study, we found a role for H(2)O(2) in UVA-induced AP-2alpha expression in the HaCaT human keratinocyte cell line. UVA irradiation not only increased AP-2alpha, but also caused accumulation of H(2)O(2) in the cell culture media, and H(2)O(2) by itself could induce the expression of AP-2alpha. By catalyzing the removal of H(2)O(2) from cells through over-expression of GPx-1, induction of AP-2alpha expression by UVA was abolished. Induction of transcription factor AP-2alpha by UVA had been previously shown to be mediated through the second messenger ceramide. We found that not only UVA irradiation, but also H(2)O(2) by itself caused increases of ceramide in HaCaT cells, and C2-ceramide added to cells induced the AP-2alpha signaling pathway. Finally, forced expression of GPx-1 eliminated UVA-induced ceramide accumulation as well as AP-2alpha expression. Taken together, these findings suggest that GPx-1 inhibits UVA-induced AP-2alpha expression by suppressing the accumulation of H(2)O(2).
authors.affiliation: Free Radical and Radiation Biology Program, Department of Radiation Oncology, Carver College of Medicine, and Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA 52242, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.forename: Sujatha
authors.initials: S
authors.lastname: Venkataraman
authors.forename: Mitchell C
authors.initials: MC
authors.lastname: Coleman
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Spitz
authors.forename: Philip W
authors.initials: PW
authors.lastname: Wertz
authors.forename: Frederick E
authors.initials: FE
authors.lastname: Domann
mesh_terms: D002518:Ceramides / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000235:genetics / Q000502:physiology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D015603:Keratinocytes / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D050656:Transcription Factor AP-2 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics; D015533:Transcriptional Activation; D014466:Ultraviolet Rays; D000094765:Glutathione Peroxidase GPX1
chemical_list: D002518:Ceramides; D050656:Transcription Factor AP-2; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human