Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1992: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
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Research Abstract |
Heme oxygenase, a key enzyme of heme degradation, is a major stress-related protein, which is induced with heme, heavy metals, heat shock, organic compounds, UV radiation, hydrogen peroxide and hypoxia. In order to elucidate the transcriptional regulation, we isolated the 4.3 kb 5' flanking region of rat heme oxygenase gene. To localize heme and cadmium responsive elements, various regions of 5' upstream sequence were fused to the cat gene, and a transient expression assay was conducted in the rat glioma cells treated with 10 mu M cadmium chloride or 10 mu M hemin. These studies indicated that the sequence from -3.3/-2.9kb was essential for the induction by cadmium. However, hemin failed to induce cat activity. Using gel sift assay, a DNA-protein complex band was observed only when nuclear extracts prepared from cadmium treated rat (14 mg/kg) were used. Our findings suggested that a transcription factor affected with cadmium binds to the region and regulates the transcription of heme oxygenase gene.
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