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The study of control technique of interspecies signal transfer

The study of control technique of interspecies signal transfer
种间信号传递控制技术研究
批准号:
08559002
负责人:
TANAKA Tomoo
金额:
$10.69万
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (A)
财政年份:
1996
资助国家:
日本
项目状态:
已结题
起止时间:
1996 至 1998

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项目成果

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中文摘要
翻译
为了检测种间信号传递的物质,我们使用了针对人脑和寄生原生动物克氏锥虫(Trypanosoma cruzi)的单克隆抗体。J.N.et al., Nature, 1982)。我们筛选了人体组织和克氏t . crozi cDNA文库,获得了几个新的基因。其中,Northern blot选择了最初通过单克隆抗体检测到的在人脑、心肌和T.cruzi中表达的新基因Bradeion。我们得到了该基因及其蛋白的结构和功能特征:1。在成人大脑中,Bradeion表达为两种类型,分别称为a型和β型。其氨基酸序列具有生长激素和细胞因子受体的基序。它也被认为是具有跨膜区和ATP/GTP结合位点的孤儿受体。2 . Northern blot只在成人大脑和心脏(占大脑的10%)显示bradjon信号,在其他组织和胚胎期均无信号。只有β型Bradejon在小鼠脑中的表达量更高(与人类Bradeion β的同源性为94%)。该基因位于小鼠染色体VH上,以3个外显子和2个内含子的形式存在,覆盖约17 kb。Bradeion α位于线粒体中,而β位于核周细胞质中。5 .转染Bradeion的人培养癌细胞发生凋亡。Bradeion基因在人培养的结直肠癌和恶性黑色素瘤癌细胞中也有表达。在人类结直肠癌和恶性黑色素瘤患者的样本中也观察到这种表达。转染反义核酶后,培养的结直肠癌细胞的生长和转化均明显降低。研究了阿尔茨海默病、亨廷顿病等神经退行性疾病的分子病理学,以控制神经细胞的衰老和预防神经细胞的死亡。基于这一研究的新药和医疗机械也在不断发展。此外,还开展了秀丽隐杆线虫、小鼠等动物模型的相关物质寻找及人体应用试验。然而,由于大脑系统的组织和细胞具有物种和个体差异,研究受到了限制。因此,有必要建立利用人类培养细胞的方法。从人类与其他生物共同进化或生物适应环境的角度出发,获得了一种与人类神经元存活(死亡)有关的新物质,即“寄生”。因此,我们的研究表明,发现了新的细胞年龄控制因子,Bradeion及其功能分析。根据这些发现,我们现在开始了以下研究,将bradion作为一个新的全球产业的种子:新型人脑孤儿受体Bradeion作为有用生理激活剂的功能分析2 .神经元非常复杂和高级结构的收缩及神经元程序性细胞死亡发生的机制分析。神经死亡控制、早期癌症诊断和癌症基因治疗的技术和医疗机械的发展。少
英文摘要
To detect the substance of interspecies signal transfer, we used the monoclonal antibody specific to human brain and parasitic protozoa, Trypanosoma cruzi (Wood. J.N.et al., Nature, 1982). We screened human tissues and T.cruzi cDNA library, and obtained several novel genes. Among them, Northern blot selected novel gene Bradeion expressing in human brain, cardiac muscle and T.cruzi, which were originally detected by the monoclonal antibody. We got the following structural and functional characterization about this gene and its protein :1. Bradeion was expressed as two types (called as a and beta) in adult human brain. The amino acid alignment of it has the motif of growth hormone and cytokine receptor. It was also considered as an orphan receptor with transmembrane region and ATP/GTP binding site.2. The signal of Bradejon in Northern blot was shown only on adult human brain and heart (10% of brain), and no signal in any other tissues and embryonic stage.3. Only beta-type of Bradejon was … More expressed in mouse brain (94% identity to human Bradeion beta). This gene is located in mouse chromosome VH and exists as 3 exons and 2 introns covering ca. 17 kb.4. Bradeion alpha was located in mitochondria and Bradeion beta in perinuclear cytoplasm.5. Apoptosis occurs in human cultured cancer cell in which Bradeion was transfected.6. Bradeion gene was also expressed in human cultured cancer cells of colorectal cancer and malignant melanoma. This expression was also observed in the samples of human colorecial cancer and malignant melanoma patients.7. The remarkable decrease of growth and the transformation in cultured colorectal cancer cell were observed when antisense ribozyme was transfected.The molecular pathology of neural degenerative disease like Alzheimer disease and Huntington disease has been studied to control the age and prevention of death of neural cell. New medicine and medical machinery based on this study are also developing now. Furthermore, the trial finding the related substance using animal models like C.elegans or mouse and its application to human have been performed. However, the study is limited by the species and individual differences, which the tissue and the cell of the cerebral system have. The establishment of the methodology to use human culture cell is therefore needed. Bradeion is quite a novel substance concerning to flue survival (death) of human neuron gained by approach from the point of view considering co-evolution of human and other organisms or adaptation of organism to environment, i. e., "parasitism".Consequently, our study demonstrated the discovery of new control factor of cell age, Bradeion and its functional analysis. According to these findings, we started the following studies to apply Bradeion as the seed of a new and global industry now :1. Analysis of function of a new human brain orphan-receptor, Bradeion as useful physiological activator.2. Analysis of the mechanism how neurons contract very complex and high-grade structure and the programmed cell death of neuron happens.3. Development of technology and medical machinery for control of neural death, diagnosis of early cancer and gene therapy of cancer. Less
期刊论文(28)
专著(0)
科研奖励(0)
会议论文
Tanaka T: "Differential Diagnosis of Trpanosoma cruzi and T.rangeli Infection by PCR of Cysteine Proteinase Genes" J Jpn Assoc Inf Dis. 71・9. 903-909 (1997)
Tanaka T:“通过半胱氨酸蛋白酶基因的PCR对克氏锥虫和兰格利锥虫感染进行鉴别诊断”J Jpn Assoc Inf Dis. 71・909。
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Tanaka M.,et al: "Schistosoma mansoni Genome Project Network" Parasitology Today. (in press). (1996)
Tanaka M.等人:“曼氏血吸虫基因组计划网络”今日寄生虫学。
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Tanaka,M.,et al: "Proceedings of Schistozoma genome Project/96" Mem.Inst.Oswald Cruz.(in press). (1996)
Tanaka,M.,et al:“裂殖虫基因组计划/96”Mem.Inst.Oswald Cruz.(正在出版)。
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25
    Study of the prevention and complementary treatment of advanced cancer: Examination of presymptomatic diagnosis and reactivation of cancer suppression mechanism
    • 批准号:
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    • 项目类别:
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    • 资助金额:
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