Xenobiotic-responsive element for the transcriptional activation of the rat Cu/Zn superoxide dismutase gene

Cu/Zn superoxide dismutase (SOD1) catalyzes the dismutation of superoxide r adicals produced from biological oxidation and environmental stresses. A nu mber of xenobiotics are toxic because they generate free radicals, such as superoxide and hydroxyl radicals, through a redox cycle. The xenobiotic res ponsive element (XRE) was located between the nt -268 and -262 region of th e 5'-flanking sequence of the SOD1 gene. Functional analyses of this elemen t by deletion, mutations, and heterologous promoter systems confirmed that the expression of the SOD1 gene was induced by a xenobiotic through the XRE . Gel mobility shift assays showed the xenobiotic inducible binding of the receptor-ligand complex to XRE. The cytoplasmic fraction from nontreated He pG2 cells also contains the factor as a cryptic form and prominently reveal s its DNA-binding activity by incubation with beta NF in vitro. These resul ts suggest that the XRE participates in the induction of the rat SOD1 gene by xenobiotics. (C) 1999 Academic Press.