Induction of gene expression via activator protein-1 in the ascorbate protection against UV-induced damage

M. Valeria Catani, Antonello Rossi, Antonio Costanzo, Stefania Sabatini, Massimo Levrero, Gerry Melino, Luciana Avigliano

Research output: Contribution to journalArticle

Abstract

UV irradiation is a major insult to the skin. We have shown previously that exogenous vitamin C (ascorbate) accmmulates in HaCaT keratinocytes, thus conferring the ability to prevent radical formation and cell death elicited by UV-B. Here, we have investigated the potential mechanisms accounting for the cytoprotective effects exerted by this antioxidant. Using a cDNA microarray hybridization, we identified several genes whose expression was up-regulated by ascorbate. We focused on the fra-1 gene, a member of the Fos family of transcription factors that down-regulates activator protein-1 (AP-1) target genes. Both in HaCaT and in normal human epidermal keratinocytes, we found Fra-1 mRNA induction as early as 2 h after ascorbate loading. Electrophoretic mobility-shift assay and antibody supershift analysis revealed that ascorbate modulates AP-1 DNA-binding activity and that Fra-1 is in AP-1 complexes in treated cells. Furthermore, transient-transfection studies, using an AP-1 reporter construct, showed that ascorbate was able to inhibit both basal and UV-B-induced AP-1-dependent transcription. Ascorbate also modulates UV-B-induced AP-1 activity by preventing the phosphorylation and activation of the upstream c-Jun N-terminal kinase (JNK), thus inhibiting phosphorylation of the endogenous c-Jun protein. These data suggest that ascorbate mediates cellular responses aimed at counteracting UV-mediated cell damage and cell death by interfering at multiple levels with the activity of the JNK/AP-1 pathway and modulating the expression of AP-1-regulated genes.

Original languageEnglish
Pages (from-to)77-85
Number of pages9
JournalBiochemical Journal
Volume356
Issue number1
DOIs
Publication statusPublished - May 15 2001

Keywords

  • Fra-1
  • JNK
  • Vitamin C

ASJC Scopus subject areas

  • Biochemistry

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