Molecular Mechanisms Involved in Oxygen Sensing by Heme.

本项目的主要目的是阐明血红素的生物学意义，特别涉及疾病的机制。今年的重要成果之一是阐明了血红素加氧酶诱导对急性肾功能衰竭的保护作用。此外，血红素代谢本身控制的副作用，肝脏疾病的发作，由氟烷。因此，探究血红素自身调控血红素代谢的机制似乎是阐明该化合物意义的关键步骤之一。虽然直到今天还没有关于哺乳动物血红素定向基因调控的显著发现，但我们发现一种新的转录因子Bach1是候选因子。我们观察了血红素调控Bach1功能的分子机制，揭示了Bach1-血红素介导的对血红素氧化酶-1基因的调控。这些研究结果发表在2000年10月17日至18日在札幌举行的环境压力下造血调节国际研讨会上（由H.Fujita主持）。在研讨会上，我们对Bach1的研究结果给予了高度评价，并将在EMBO杂志上发表。

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.