TY - JOUR
T1 - Transcriptional Regulation of the Antioxidant Protein 2 Gene, a Thiol-specific Antioxidant, by Lens Epithelium-derived Growth Factor to Protect Cells from Oxidative Stress
AU - Fatma, Nigar
AU - Singh, Dhirendra P.
AU - Shinohara, Toshimichi
AU - Chylack, Leo T.
PY - 2001/12/28
Y1 - 2001/12/28
N2 - Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H202 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.
AB - Antioxidant protein 2 (AOP2), a member of the newly defined family of thiol-specific antioxidant proteins, has been shown to remove H202 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.
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U2 - 10.1074/jbc.M100733200
DO - 10.1074/jbc.M100733200
M3 - Article
C2 - 11677226
AN - SCOPUS:0035966103
SN - 0021-9258
VL - 276
SP - 48899
EP - 48907
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 52
ER -