English  |  正體中文  |  简体中文  |  Items with full text/Total items : 54371/62179 (87%)
Visitors : 8916168      Online Users : 116
RC Version 6.0 © Powered By DSPACE, MIT. Enhanced by NTHU Library IR team.
Scope Tips:
  • please add "double quotation mark" for query phrases to get precise results
  • please goto advance search for comprehansive author search
  • Adv. Search
    HomeLoginUploadHelpAboutAdminister Goto mobile version
    National Tsing Hua University Institutional Repository > 生命科學院  > 分子醫學研究所 > 博碩士論文 >  肌間線蛋白之肌病性突變引起絲狀聚集與潛在Caspase-6活化和粒線體型態變化


    Please use this identifier to cite or link to this item: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/85647


    Title: 肌間線蛋白之肌病性突變引起絲狀聚集與潛在Caspase-6活化和粒線體型態變化
    Authors: 林彥廷
    Description: GH02101080528
    碩士
    分子醫學研究所
    Date: 2014
    Keywords: 肌間線蛋白;粒線體;肌間線蛋白肌病變
    desmin;mitochondria;desmin-related myopathy;caspase-6;aggregation
    Abstract: Caspase cleavage of several intermediate filament (IF) proteins generates proteolytic fragments that characterize apoptosis as shown for lamins and vimentin. These fragments affect IF assembly in a way that promotes filament aggregation. The hypothesis is that disease-causing mutations in IF proteins and subsequent characteristic histopathological aggregates could involve caspase cleavage of IF proteins. Desmin is a type III IF protein that is expressed mainly in the muscle cells. Heterozygous missense mutations in the desmin gene cause desmin-related myopathy (DRM), a progressive muscle wasting disease. The pathological hallmark of DRM is cytoplasmic desmin-containing aggregates in skeletal and cardiac muscles. The expression of mutant desmin induced filament aggregation and mitochondrial clumping. Accompanied with these changes were caspase activation and desmin proteolysis. In this study, I have demonstrated that desmin is cleaved specifically by caspase-6 at VEMD263 and produces two major cleavage products. While the C-terminal desmin (C-desmin) is unable to assemble into filaments, the N-terminal desmin (N-desmin) forms aggregates and interfere with normal IF assembly. When transiently expressed into a range of cultured cell lines, N-desmin formed cytoplasmic aggregates that also disrupted the endogenous IF networks of desmin, consistent with its effect in vitro. In addition, I have generated a neo-epitope antibody that recognized caspase-cleaved but not the intact desmin. This antibody revealed the presence of the N-desmin in a subset of transfected cells expressing myopathic desmin mutants. Furthermore, expression of mutants induces a cellular stress response and alters mitochondrial morphology. Taken together, these data suggest that the integrity of IF is a key sensor for cell homeostasis and their functional interaction with mitochondria and cell death signaling pathway are central to the progressive muscle degeneration seen in human desminopathies.
    URI: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/85647
    Source: http://thesis.nthu.edu.tw/cgi-bin/gs/hugsweb.cgi?o=dnthucdr&i=sGH02101080528.id
    Appears in Collections:[分子醫學研究所] 博碩士論文

    Files in This Item:

    File SizeFormat
    GH02101080528.pdf108KbAdobe PDF94View/Open


    在NTHUR中所有的資料項目都受到原著作權保護,僅提供學術研究及教育使用,敬請尊重著作權人之權益。若須利用於商業或營利,請先取得著作權人授權。
    若發現本網站收錄之內容有侵害著作權人權益之情事,請權利人通知本網站管理者(smluo@lib.nthu.edu.tw),管理者將立即採取移除該內容等補救措施。

    SFX Query

    與系統管理員聯絡

    DSpace Software Copyright © 2002-2004  MIT &  Hewlett-Packard  /   Enhanced by   NTU Library IR team Copyright ©   - Feedback