An Attempt to Identify Amyloid Precursor Protein Processing Pathway Involving Lysosomal System by Vesicle Specific Protein
通过囊泡特异性蛋白鉴定涉及溶酶体系统的淀粉样前体蛋白加工途径的尝试
基本信息
- 批准号:07671080
- 负责人:
- 金额:$ 1.47万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1995
- 资助国家:日本
- 起止时间:1995 至 1996
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The lysosomal pathway has been suggested as the site of formation for amyloidogenic amyloid precursor protein (APP) fragment and amyloid beta protein (Abeta). Lysosomes are, however, meeting places in which several streams of intracellular traffic converge. We describe here an attempt to identify APP processing pathway involving lysosomal system by vesicle specific protein1. Antibodies raised against transport vesicle specific proteins : There are clathrin-coated vesicle, and non-clathrin coated vesicle, designated as coatmer protein-coated vesicle of transport vesicles. We were successful in raising antibodies against synthetic peptides homologous to amino acid sequence of clathrin, and beta-COP.2. Proteolytic processing of APP in cultured human myocyte treated with/without concanamycin A (Con A) : Con A inhibits selectively endocytosis from cell surface to intracsllular compartments via clathrin-coated vesicles.1) Histopathological studies of cultured myocytes : Vacuoles appeared ben … More eath the plasma membrane in the cultured myocytes 12 hours after Con A treatment, and increase in number until up to 24 hours.2) Immunopathological studies of APP and Abeta localization : Con A induced vacuoles were labeled with anti-APP,and anti-Abeta antibodies. A number of these vacuoles were also atained with clathrin antibody. Interestingly, beta-COP antibody labeled unique dot-like structures in the cytoplasm without Con A treatment. Cultured myocytes treated with Con A,vacuoles were labeled with beta-COP antibody. But no immunoreactivities were observed with anti-ERGIC 53, specific for endoplasmic reticulum, and with anti-garactosyltransferase, specific protein to Golgi apparatus.3. Biochemical studies on proteolytic processing of APP : Metabolic labeling of cultured myocytes were performed of cultured myocytes treated with/without Con A.APP and Abeta in the cell lysates were immunoprecipitated with specific antibodies against APP,and Abeta. Subsequently, eluates were separated on electrophoresis, and then subjected to autoragiography. 4 kDa Abeta fragment was detected in cell lysate without Con A treatment, and this 4 kDa Abeta fragment increased their intensity after Con A treatment.Our data indicate that non-clathrin coated vesicles to acidic compartments, lysosomes, may play an important role in the generation of amyloidogenic fragments and Abeta, in addition to clathrin-coated vesicles. Less
溶酶体途径被认为是淀粉样变性淀粉样前体蛋白(APP)片段和淀粉样β蛋白(Abeta)的形成部位。然而,溶酶体是几个细胞内流量汇聚的地方。在这里,我们描述了一种尝试,以确定囊泡特异性蛋白1涉及溶酶体系统的APP处理途径。抗运输囊泡特异性蛋白抗体:有包被蛋白的囊泡,也有非包被蛋白的囊泡,称为被膜蛋白包被的囊泡。我们成功地制备了与笼状蛋白氨基酸序列同源的合成肽和β-COP2的抗体。刀豆蛋白A对培养的人心肌细胞APP的蛋白降解作用:刀豆素A选择性地抑制从细胞表面到细胞内的内吞作用1)培养心肌细胞的组织病理学研究:Ben…出现空泡培养的心肌细胞在ConA处理12小时后,质膜上有更多的APP和Aβ的定位。2)APP和Aβ定位的免疫病理研究:用抗APP和抗Aβ的抗体标记ConA诱导的空泡。这些空泡中的许多也被抗网状蛋白抗体所标记。有趣的是,在没有ConA处理的情况下,β-COP抗体标记了细胞质中独特的点状结构。用ConA处理培养的心肌细胞,用β-COP抗体标记空泡。而内质网特异性抗ERGIC53和高尔基体特异性蛋白抗半乳糖基转移酶均未见免疫反应。APP蛋白分解过程的生化研究:培养的心肌细胞经ConA处理前后进行代谢标记,细胞裂解液中APP和Abeta与APP和Abeta的特异性抗体免疫共沉淀。随后,洗脱液在电泳法上分离,然后进行自显影。在没有ConA处理的细胞裂解液中检测到4 kDa的Abeta片段,该4 kDa的Abeta片段在ConA处理后增强了其强度。我们的数据表明,在淀粉样蛋白原片段和Abeta的产生过程中,除了被Con A处理的囊泡外,非笼络蛋白包裹的囊泡可能在酸性隔室的溶酶体中发挥重要作用。较少
项目成果
期刊论文数量(39)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Tsuzuki K et al: "Chloroquine-induced myopathy as a possible model for Alzheimer's disease." Ronenkichihoukenkyukaishi. 9. 1-5 (1996)
Tsuzuki K 等人:“氯喹诱导的肌病是阿尔茨海默病的可能模型。”
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Tsuzuki K et al: "Amyloid beta protein and transthyretin, sequestraing protein colocalize in normal human kidney." Neuroscience Letters. 222. 163-166 (1997)
Tsuzuki K 等人:“β 淀粉样蛋白和转甲状腺素蛋白、隔离蛋白共存于正常人肾脏中。”
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- 影响因子:0
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Tsuzuki K et al: "Immunohistochemical evidence for Aβ40 and Aβ42 in rat soleus muscle in chloroquine-induced myopathy" Neurobiology of Aging. 17. 63 (1996)
Tsuzuki K 等人:“氯喹诱导的肌病中大鼠比目鱼肌中 Aβ40 和 Aβ42 的免疫组织化学证据”《衰老神经生物学》17. 63 (1996)。
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高丸勇司、深津 亮他: "老人斑アミロイドのアポリポプロテインE" 老年精神医学雑誌. 6. 1129-1137 (1995)
Yuji Takamaru、Ryo Fukatsu 等人:“老年斑淀粉样蛋白中的载脂蛋白 E”《老年精神病学杂志》6. 1129-1137 (1995)。
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- 影响因子:0
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Tsuzuki K et al: "Co-localization of amyloid associated proteins with amyloid beta in rat soleus muscle in chloroquine-induced myopathy : a possible model for amyloid beta formation in Alzheimer's disease." Brain Research. 699. 260-265 (1995)
Tsuzuki K 等人:“在氯喹诱导的肌病中,淀粉样蛋白相关蛋白与淀粉样蛋白 β 在大鼠比目鱼肌中的共定位:阿尔茨海默病中淀粉样蛋白 β 形成的可能模型。”
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TAKAHATA Naohiko其他文献
TAKAHATA Naohiko的其他文献
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{{ truncateString('TAKAHATA Naohiko', 18)}}的其他基金
Molecular Biological Studies on Processing of Amyloid Precursor Protein in Lysosomal Pathway
淀粉样前体蛋白在溶酶体途径中加工的分子生物学研究
- 批准号:
05670817 - 财政年份:1993
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
MOLECULAR BIOLOGICAL STUDIES OF APP PROCESSING
APP 处理的分子生物学研究
- 批准号:
03670568 - 财政年份:1991
- 资助金额:
$ 1.47万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
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