Molecular Mechanisms Involved in Oxygen Sensing by Heme.

血红素参与氧传感的分子机制。

• 批准号: 10044230
• 负责人: FUJITA Hiroyoshi
• 金额: $ 6.91万
• 依托单位: Hokkaido University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10044230/
• 关键词: Heme; Oxygen Sensing; Heme Oxygenase; Transcription; 遺伝性ヘモクロマトージス; 晩発性皮膚ポルフィリン症; 鉄芽球性貧血患者; HLA-B27; ヘムオキシゲナーゼ-1; 赤血球系; ヘム合成系; 環境応答

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.

本计画的主要目的是阐明血红素的生物学意义，特别是疾病的发生机制。今年的重要成果之一是阐明血红素加氧酶诱导对急性肾衰竭的保护作用。此外，血红素代谢本身控制氟烷的副作用--肝脏疾病的发生，因此，血红素自身调节血红素代谢的机制似乎是阐明氟烷的重要性的关键步骤之一。虽然到目前为止还没有关于哺乳动物中血红素介导的基因调控的显著发现，但我们发现了一个新的转录因子Bach 1，它是候选者。我们观察了血红素调节Bach 1功能的分子机制，揭示了Bach 1-血红素介导的血红素加氧酶-1基因的调控，这些发现在2000年10月17 - 18日在札幌召开的国际研讨会上发表。在这次研讨会上，我们对Bach 1的研究结果给予了高度评价，目前该研究结果将在EMBO J.

项目成果

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K. Furuyama 等人：“日本铁粒幼细胞性贫血患者的血色素沉着症基因不存在 C282Y 和 H63D 突变”Amer。

藤田博美、竹谷茂ほか: "環境変動と分子応答" 環境科学会誌. 11. 183-192 (1998)

Hiromi Fujita、Shigeru Takeya 等人：“环境波动和分子反应”环境科学学会杂志 11. 183-192 (1998)。

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Y.Okada,T.Takahashi A.Yamasaki 等人：“通过氯化血红素预处理预防氟烷诱导的肝毒性。”Biochem.Pharmacol.. 59. 871-880 (2000)

T.Nagai,K.Igarashi,J.Akasaka et al.: "Regulation of NF-E2 Activity in Erythroleukemia Cell Differentiation." J.Biol.Chem.278. 5358-5365 (1998)

T.Nagai、K.Igarashi、J.Akasaka 等人：“红白血病细胞分化中 NF-E2 活性的调节”。

K. Takahashi, et al.: "Suppression of heme oxygenase-1 mRNA expression by interferon-g in human glioblastoma cells"J. Neurochem. 72. 2356-2361 (1999)

K. Takahashi 等人：“干扰素-g 在人胶质母细胞瘤细胞中抑制血红素加氧酶-1 mRNA 表达”J.