In this study, we found a role for H2O2 in UVA-induced AP-2 alpha expression in the HaCaT human keratinocyte cell line. UVA irradiation not only increased AP-2 alpha, but also caused accumulation of H2O2 in the cell culture media, and H2O2 by itself could induce the expression of AP-2 alpha. By catalyzing the removal of H2O2 from cells through over-expression of GPx-1, induction of AP-2 alpha expression by UVA was abolished. Induction of transcription factor AP-2 alpha by UVA had been previously shown to be mediated through the second messenger ceramide. We found that not only UVA irradiation, but also H2O2 by itself caused increases of ceramide in HaCaT cells, and C2-ceramide added to cells induced the AP-2 alpha signaling pathway. Finally, forced expression of GPx-1 eliminated UVA-induced ceramide accumulation as well as AP-2 alpha expression. Taken together, these findings suggest that GPx-1 inhibits UVA-induced AP-2 alpha expression by suppressing the accumulation of H2O2. (c) 2006 Elsevier Inc. All rights reserved.