UV irradiation is a major insult to the skin. We have shown previously that exogenous vitamin C (ascorbate) accumulates 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 2h 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.
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Research Article|
May 08 2001
Induction of gene expression via activator protein-1 in the ascorbate protection against UV-induced damage
M. Valeria CATANI;
M. Valeria CATANI
∗Biochemistry Laboratory, IDI-IRCCS, c/o Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy
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Antonello ROSSI;
Antonello ROSSI
†Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy
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Antonio COSTANZO;
Antonio COSTANZO
‡Laboratory of Gene Expression, Fondazione A. Cesalpino, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy
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Stefania SABATINI;
Stefania SABATINI
†Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy
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Massimo LEVRERO;
Massimo LEVRERO
‡Laboratory of Gene Expression, Fondazione A. Cesalpino, University of Rome La Sapienza, Viale del Policlinico 155, 00161 Rome, Italy
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Gerry MELINO;
Gerry MELINO
†Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy
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Luciana AVIGLIANO
Luciana AVIGLIANO
1
†Department of Experimental Medicine & Biochemical Sciences, University of Rome Tor Vergata, Via di Tor Vergata 135, 00133 Rome, Italy
1To whom correspondence should be addressed (e-mail avigliano@uniroma2.it).
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Publisher: Portland Press Ltd
Received:
October 26 2000
Revision Received:
February 07 2001
Accepted:
March 19 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2001
2001
Biochem J (2001) 356 (1): 77–85.
Article history
Received:
October 26 2000
Revision Received:
February 07 2001
Accepted:
March 19 2001
Citation
M. Valeria CATANI, Antonello ROSSI, Antonio COSTANZO, Stefania SABATINI, Massimo LEVRERO, Gerry MELINO, Luciana AVIGLIANO; Induction of gene expression via activator protein-1 in the ascorbate protection against UV-induced damage. Biochem J 15 May 2001; 356 (1): 77–85. doi: https://doi.org/10.1042/bj3560077
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