Heavy metal-mediated activation of the rat Cu/Zn superoxide dismutase gene via a metal-responsive element.
The Cu/Zn superoxide dismutase (SODI) catalyzes the dismutation of superoxide radicals produced in the course of biological oxidations. When placed under the control of the rat SOD1 gene promoter and transfected into human HepG2 hepatoma cells, the activity of a chloramphenicol acetyltransferase reporter gene was found to increase three- to four-fold in the presence of heavy metals (cadmium, zinc and copper). Functional analysis of mutant derivatives of the SOD1 gene promoter and the use of a heterologous promoter system confirmed that the induction of the SOD1 gene by metal ions requires a metal-responsive element (MRE) located between positions -273 and -267 (GCGCGCA). It was also shown by gel mobility shift assays that an MRE binding protein is induced by the exposure of the human liver cell line HepG2 to heavy metals. These results suggest that the MRE participates in the induction of the SOD1 gene by heavy metals.
Yoo
H Y
HY
Department of Molecular Biology, Research Center for Cell Differentiation, Seoul National University, Korea.
Chang
M S
MS
Rho
H M
HM
D000818:Animals; D002104:Cadmium; D004268:DNA-Binding Proteins; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D051381:Rats; D020218:Response Elements; D013482:Superoxide Dismutase / Q000235:genetics*; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D000097809:Transcription Factor MTF-1
D002104:Cadmium; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014157:Transcription Factors; D000097809:Transcription Factor MTF-1; C000606290:SOD1 protein, human; C000606292:Sod1 protein, rat