The activation of the rat copper/zinc superoxide dismutase gene by hydrogen peroxide through the hydrogen peroxide-responsive element and by paraquat and heat shock through the same heat shock element.
Copper/zinc superoxide dismutase (SOD1) protects cells against oxidative hazards by the dismutation of superoxide radicals. The promoter activity of the SOD1 gene was increased 3-5-fold by hydrogen peroxide, paraquat (PQ) and heat shock. Functional analyses of the regulatory region of the SOD1 gene by deletions, mutations, and heterologous promoter systems confirmed the induction of the SOD1 gene by H(2)O(2) through the hydrogen peroxide-responsive element (HRE) (between nucleotides -533 and -520). Gel mobility shift assays showed that the existence of an H(2)O(2)-inducible protein bound to the oligonucleotide of the HRE. Similar analyses showed that the heat shock activated the SOD1 promoter through the heat shock element (HSE) (between nucleotides -185 and -171). A strong specific far-shifted complex with the oligonucleotide of the HSE was observed by the treatment of heat shock. When cells were treated with PQ, a strong far-shifted complex with the HSE was observed and was competed out by the cold HSE probe, indicating that PQ also activated the SOD1 promoter through the same HSE site. It is very interesting to note that chemical and physical stresses, such as PQ and heat shock, respectively, activated the SOD1 promoter through the same cis-element HSE. These results indicate that the SOD1 was inducible by H(2)O(2) through the HRE and by PQ and heat shock through the same HSE to protect cells from oxidative hazards.
Yoo
H Y
HY
Department of Molecular Biology and Research Center for Cell Differentiation, Seoul National University, Seoul 151-742, Korea.
Chang
M S
MS
Rho
H M
HM
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D010269:Paraquat / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D051381:Rats; D020218:Response Elements / Q000502:physiology*; D013482:Superoxide Dismutase / Q000235:genetics*; D013481:Superoxides / Q000378:metabolism; D014157:Transcription Factors
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D014157:Transcription Factors; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010269:Paraquat