Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene

摘要: Twenty-four base pairs of the human antioxidant response element (hARE) are required for high basal transcription NAD(P)H:quinone oxidoreductase1 (NQO1) gene and its induction in to xenobiotics antioxidants. hARE is a unique cis-element that contains one perfect imperfect AP1 arranged as inverse repeats separated by 3 bp, followed “GC” box. We report here Jun, Fos, Fra, Nrf nuclear factors bind hARE. Overexpression cDNA derived combinations proteins Jun Fos or Fra1 repressed hARE-mediated chloramphenicol acetyltransferase (CAT) expression transfected hepatoblastoma (Hep-G2) cells. Further experiments suggested this repression was due overexpression c-Fos Fra1, but not proteins. The (c-Jun, Jun-B, Jun-D) all possible were more less ineffective upregulation expression. Interestingly, Nrf1 Nrf2 individually Hep-G2 monkey kidney (COS1) cells significantly increased CAT from reporter plasmid hARE-thymidine kinase-CAT inducible β-naphthoflavone tert-butyl hydroquinone. These results indicated NQO1 antioxidants mediated Nrf2. expression, however, Fra1.