Molecular Mechanisms Involved in Oxygen Sensing by Heme.

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Main aim of this project is to elucidate the biological significances of heme, with special reference to the mechanisms of diseases. One of the important results of this year is the elucidation of protective effect of heme oxygenase induction against acute renal failue. In addition, heme metabolism itself controlled the onset of side effect, hepatic disorder, by halothane.Therefore, the mechanism to regulate heme metabolism by heme itself seems to be one of the key step to elucidate the significance of the compound. Although no remarkable finding about the heme-directed gene regulation in mammals has been reported until today, we found a new transcription factor, Bach1, is the candidate. We observed the molecular mechanism of heme to regulate Bach1 fanction and revealed the Bach1-heme mediated control ofheme oxygenase-1 gene.These findings were presented in the International Symposium on the Regulation of Hematopoiesis in response to Environmental stress, held in Sapporo, from October 17 to 18, 2000 (chaired by H.Fujita). In the symposium, our findings on Bach1 is highly evaluated, and nowadays it is going to in press in the EMBO J.