Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress.

Abstract	Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H(2)O(2) and protect proteins and DNA from oxidative stress. Here we report that LEDGF is one of the regulatory factors for the AOP2 gene. We found that LEDGF bound to the heat shock element and to stress-related elements in the AOP2 promoter. It trans-activated expression of AOP2-CAT in COS-7 cells and lens epithelial cells overexpressing LEDGF. Mutations in the heat shock element and stress-related elements of the AOP2 promoter reduced LEDGF-dependent trans-activation. Lens epithelial cells showed a higher level of AOP2 mRNA in the presence of LEDGF. Cells overexpressing LEDGF exhibited a higher level of AOP2 protein, the level of which was directly related to the increase in cellular protection. Thus, LEDGF, by activating the AOP2 gene, protected and enhanced the survival of cells under oxidative stress.
Authors	N Fatma, D P Singh, T Shinohara, L T Chylack Jr
Journal	The Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 52 Pg. 48899-907 (Dec 28 2001) ISSN: 0021-9258 [Print] United States
PMID	11677226 (Publication Type: Journal Article)
Chemical References	Antioxidants Growth Substances Intercellular Signaling Peptides and Proteins Oxidants Proteins RNA, Messenger Recombinant Fusion Proteins lens epithelium-derived growth factor Hydrogen Peroxide Peroxidases PRDX6 protein, human Peroxiredoxin VI Peroxiredoxins
Topics	Animals Antioxidants (metabolism) Base Sequence COS Cells DNA Footprinting Dose-Response Relationship, Drug Epithelial Cells (cytology, metabolism) Gene Expression Regulation Genes, Reporter Growth Substances (metabolism) HeLa Cells Humans Hydrogen Peroxide (metabolism) Intercellular Signaling Peptides and Proteins Lens, Crystalline (cytology, metabolism) Molecular Sequence Data Oxidants (metabolism) Oxidative Stress (physiology) Peroxidases Peroxiredoxin VI Peroxiredoxins Promoter Regions, Genetic Protein Binding Proteins (genetics, metabolism) RNA, Messenger (metabolism) Recombinant Fusion Proteins (metabolism) Transcriptional Activation

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