The study of control technique of interspecies signal transfer
The study of control technique of interspecies signal transfer
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
中文摘要
为了检测物种间信号传递的物质,我们使用了针对人脑和寄生原虫的单抗。J.N.et等,《自然》,1982)。我们对人体组织和克氏锥虫的cDNA文库进行了筛选,获得了几个新的基因。其中,Northern杂交选择了在人脑、心肌和克氏毛滴虫中表达的新基因Bradeion,这些基因最初是通过单抗检测到的。我们获得了该基因及其蛋白的结构和功能特征如下:1.Bradeion在成人脑中表达为两种类型(称为α和β)。其氨基酸序列具有生长激素和细胞因子受体的基序。它也被认为是一个具有跨膜区和ATP/GTP结合位点的孤儿受体。Northern印迹显示Bradejon仅在成人脑和心脏(占脑的10%)有信号,其他组织和胚胎期均无信号。唯一的测试型Bradejon是…在小鼠脑中表达更多(94%与人类Bradeion beta相同)。该基因位于小鼠染色体VH中,以3个外显子和2个内含子形式存在,全长约17kb.4。Bradeionα位于线粒体,Bradeionβ位于核周细胞质。转导Bradeion基因的人癌细胞发生了细胞凋亡。Bradeion基因在培养的人结直肠癌和恶性黑色素瘤癌细胞中也有表达。在人类色素细胞癌和恶性黑色素瘤患者的样本中也观察到了这种表达。转导反义核酶后,培养的结直肠癌细胞生长和转化明显减慢。为了控制神经细胞的年龄,防止神经细胞死亡,我们对阿尔茨海默病和亨廷顿病等神经退行性疾病的分子病理学进行了研究。基于这项研究的新药物和医疗机械目前也在开发中。此外,还进行了利用线虫或小鼠等动物模型寻找相关物质的试验,并将其应用于人类。然而,这项研究受到大脑系统组织和细胞的种类和个体差异的限制。因此,建立使用人类培养细胞的方法学是必要的。Bradeion是一种与人类神经元存活(死亡)有关的新物质,它是从人类与其他生物的共同进化或生物对环境的适应角度获得的,即“寄生”。因此,我们的研究证实了新的细胞年龄控制因子Bradeion的发现及其功能分析。根据这些发现,我们现在开始了以下研究,以应用Bradeion作为一个新的全球产业的种子:1.分析新的人脑孤儿受体Bradeion作为有用的生理激活剂的功能。分析神经元如何收缩非常复杂的高级结构和神经元的程序性细胞死亡的发生机制。控制神经死亡、早期癌症诊断和癌症基因治疗的技术和医疗机械的发展。较少
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
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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: "The Triplet Repcat(Alanine;GCT)in Ribosomal Protein L14 of Immortalized Human Endothelial Cell Line(t-HUEA)." Biochemical and Biophysical Research Communications. (in press). (1998)
Tanaka M:“永生化人内皮细胞系 (t-HUEA) 核糖体蛋白 L14 中的三联体 Repcat(丙氨酸;GCT)。”
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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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Tanaka M: "The Triplet Repeat (Alanine ; GCT) in Ribosomal Protein L14 of Immortalized Human Endothelial Cell Line (t-HUE4)." Biochemical and Biophysical Research Communications. 243・2. 531-537 (1998)
田中 M:“永生化人内皮细胞系 (t-HUE4) 核糖体蛋白 L14 中的三联体重复序列(丙氨酸;GCT)”,《生物化学和生物物理研究通讯》243·2。
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共 25 条
Study of the prevention and complementary treatment of advanced cancer: Examination of presymptomatic diagnosis and reactivation of cancer suppression mechanism
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批准号:16K09258
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$3.08万
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财政年份:2016
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负责人:TANAKA Tomoo
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依托单位:
The study of the development of anti-cancer drug which targets human septin 4 (Bradeion) GTPase
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批准号:22501052
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.75万
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财政年份:2010
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负责人:TANAKA Tomoo
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依托单位:
Development of cancer therapeutic technology by functional measurement and control of cell division.
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批准号:18590540
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$2.53万
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财政年份:2006
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负责人:TANAKA Tomoo
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依托单位:
Development of monitoring system of colorectal cancer
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批准号:15590499
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项目类别:Grant-in-Aid for Scientific Research (C)
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资助金额:$1.92万
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财政年份:2003
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负责人:TANAKA Tomoo
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依托单位:
海外基金