Transcriptional activation of the human Cu/Zn superoxide dismutase gene by 2,3,7,8-tetrachlorodibenzo-p-dioxin through the xenobiotic-responsive element.
Cu/Zn superoxide dismutase (SOD1) catalyzes the dismutation of superoxide radicals produced during biological oxidations and environmental stress. Here we have investigated the effect of the most toxic dioxin, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), on the promoter of the Cu/Zn superoxide dismutase (SOD1) gene in HepG2 and HeLa cells using the chloramphenicol acetyltransferase gene as a reporter. The SOD1 promoter was activated 4- to 5-fold by TCDD treatment, in a concentration-dependent manner. In addition, the level of SOD1 mRNA and the enzymatic activity of the SOD1 protein were also enhanced on exposure of the cells to TCDD. Functional analysis of the regulatory region of the SOD1 gene by deletion and point mutation, and the use of a heterologous promoter system, showed that the SOD1 gene was transactivated by TCDD via the xenobiotic-responsive element (XRE). Gel mobility shift assays also confirmed the induction and the inducible binding of a receptor-ligand complex to XRE. Yeast cells that overexpress hSOD1 appeared to be more resistant to TCDD than the wild type. These results demonstrate that SOD1 is induced by TCDD via the XRE. The induced SOD1 may accelerate the neutralization of the superoxide anion and thus reduce the oxidative damage associated with dioxin toxicity.
Cho
J S
JS
School of Biological Sciences, Seoul National University, Korea.
Chang
M S
MS
Rho
H M
HM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D018384:Oxidative Stress; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics*; D015533:Transcriptional Activation / Q000187:drug effects*; D015262:Xenobiotics / Q000378:metabolism / Q000494:pharmacology*
D017931:DNA Primers; D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D013482:Superoxide Dismutase; D015500:Chloramphenicol O-Acetyltransferase