Transcriptional regulation of the antioxidant protein 2 gene, a thiol-specific antioxidant, by lens epithelium-derived growth factor to protect cells from oxidative stress.
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.
Fatma
N
N
Center for Ophthalmic Research, Department of Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Singh
D P
DP
Shinohara
T
T
Chylack
L T
LT
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001483:Base Sequence; D019556:COS Cells; D018983:DNA Footprinting; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006133:Growth Substances / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D007908:Lens, Crystalline / Q000166:cytology* / Q000378:metabolism; D008969:Molecular Sequence Data; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D010544:Peroxidases; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015533:Transcriptional Activation
D000975:Antioxidants; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D016877:Oxidants; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C119380:lens epithelium-derived growth factor; D006861:Hydrogen Peroxide; D010544:Peroxidases; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins