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Regulation of transcription by heme with sperm reference to cell differentiation

Regulation of transcription by heme with sperm reference to cell differentiation
血红素对精子转录的调节与细胞分化有关
批准号:
14370048
负责人:
FUJITA Hiroyoshi
金额:
$7.62万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2002
资助国家:
日本
项目状态:
已结题
起止时间:
2002 至 2004

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中文摘要
翻译
我们研究了第一个发现的含血红素的哺乳动物转录因子Bach 1。我们以前的研究表明,该因子含有一摩尔血红素每一个亚基,和Bach 1的DNA结合活性是负调控血红素饱和。也就是说,血红素饱和的Bach 1失去了与MARE位点的结合活性,从而为Nrf 2、NFE 2等转录因子提供了MARE位点。在本研究中,我们检测了母鸡加氧酶-1基因是否受Bach 1/血红素系统的控制,该基因是由其底物激活的,是家猫的关键酶。正如我们所预期的那样,我们的数据清楚地表明血红素加氧酶-1基因通过Bach 1与MARE位点的结合而受到负调控。因此,我们首次阐明了在此介导的基因激活的确切机制,该基因在生理上对代谢大量血红素(一种生物有害的促氧化剂)具有重要意义。除了血红素加氧酶-1基因外,我们还研究了β-珠蛋白基因的调控。众所周知,血红蛋白的血红素和球蛋白合成是协调的;即,血红素和珠蛋白的合成没有超标。血红素和球蛋白等摩尔的调节机制还不清楚。Bach 1是控制血红蛋白形成的最可能机制之一。事实上,我们的观察表明,在珠蛋白基因的MEAR位点规则血红素介导的上调通过Bach 1结合活性的损失。因此,我们可以生物合成珠蛋白蛋白,就等于在分化红系细胞。通过这种方式,我们免于危险的促氧化剂,血红素,甚至通过红细胞分化。
英文摘要
We have investigated Bach1, the first found mammalian transcriptional factor that contains heme. Our previous investigations reveals that the factor contains one mole of heme per one subunit, and that the DNA binding activity of Bach1 is negatively regulated by heme saturation. In other words, heme saturated Bach1 lose its binding activity against MARE site resulting in an available MARE site for another transcriptional factors such as Nrf2, NFE2 and so on.It has been, however, not yet well elucidated the genes that are under the negative control in Bach1/heme system. In the present study, we have examined if hens oxygenase-1 gene, the key enzyme of home catabolism, which is well known to activated by its substrate, is under the control of Bach1/heme system or not. As was already expected, our data is clearly indicated that heme oxygenase-1 gene was negatively regulated through Bach1 binding to MARE site. Hereby, we elucidated for the first time the precise mechanism of here mediated activation of gene that is physiologically important to metabolize a huge amount of heme, a biologically harmful pro-oxidant.In addition to heme oxygenase-1 gene, we have examined the regulation of beta-globin gene. It is well known that heme and globin syntheses for hemoglobin are coordinated ; i.e., there are no exceeded syntheses for heme and globin. The mechanism to regulate equal mole of heme and globin has not been well understood. Bach1 is one of the most possible mechanisms to control hemoglobin formation. Indeed, our observations demonstrated that MEAR site in globin gene ruled heme mediated upregulation via the loss of Bach1 binding activity. Thus, we can biosynthesize globin protein just equal to home in differentiating erythroid cells. In this way, we are free form dangerous pro-oxidant, heme, even through erythroid differentiation.
期刊论文(49)
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会议论文
The effect of Au injection on the ceruloplasmin, metallothionein and 8-hydroxydeoxyguanosine of rat serum, kidney and liver.
金注射液对大鼠血清、肾脏和肝脏铜蓝蛋白、金属硫蛋白和8-羟基脱氧鸟苷的影响。
DOI: --
发表时间: 2002
期刊: Chemico-Biological Interactions 140
影响因子: --
作者: [Saito S, Hiyamuta S, Kurasaki M, Hosokawa T, Saito T, Fujita H, Yoshida K]
通讯作者: Yoshida K
DOI: 10.1182/blood-2003-04-1319
发表时间: 2005-04-15
期刊: BLOOD
影响因子: 20.3
作者: [Oda, A, Miki, H, Takenawa, T]
通讯作者: Takenawa, T
Calpin is a STAT3 and STAT5 protease.
Calpin 是一种 STAT3 和 STAT5 蛋白酶。
DOI: --
发表时间: 2002
期刊: Blood 99
影响因子: --
作者: [Oda A et al.]
通讯作者: Oda A et al.
Y.Yasuda, Y.Fujita, S.Masuda et al.: "Erythropoietin is involved in growth and angiogenesis in malignant tumors of female reproductive organs"Carcinogenesis. 23巻. 1797-1805 (2002)
Y.Yasuda、Y.Fujita、S.Masuda 等:“促红细胞生成素参与女性生殖器官恶性肿瘤的生长和血管生成”《癌发生》23. 1797-1805 (2002)。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
共 26 条
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    Molecular Mechanisms Involved in Oxygen Sensing by Heme.
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      10044230
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      Grant-in-Aid for Scientific Research (B).
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