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    National Tsing Hua University Institutional Repository > 生命科學院  > 分子與細胞生物研究所 > 博碩士論文  >  B型肝炎病毒的感染對於粒線體動態行為之調控及其生理意義

    Please use this identifier to cite or link to this item: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/86856

    Title: B型肝炎病毒的感染對於粒線體動態行為之調控及其生理意義
    Authors: 周明慧
    Chou, Ming Hui
    Description: GH02102080529
    Date: 2015
    Keywords: B型肝炎病毒 粒線體 粒線體動態平衡
    Hepatitis B Virus (HBV) Mitochondria Mitochondrial Dynamics
    Abstract: 肝癌是全球常見的癌症之一,形成肝癌許多危險因子中,B型肝炎病毒感染和肝癌的發展有高度相關。粒線體是調控細胞許多功能的重要胞器,包括ATP的生成、細胞代謝、鈣離子濃度穩態、活性氧分子信號途徑、以及細胞生存等。粒線體進行融合和分裂的動態,能夠維持粒線體的數量、生物質量、型態和功能。先前,許多研究已經指出HBx突變和pre-S突變在肝癌形成中扮演重要角色,除此,HBx已經被證實會促使粒線體動態的不平衡,然而,顯少研究致力於LHBs和粒線體之間的關聯。本研究中,我們目的是探討LHBs對於粒線體動態平衡的調控機制,以及其生理意義。我們發現,在肝癌細胞中,HBV或LHBs會透過Drp1使得粒線體的動態平衡偏向分裂(Fission),然而,在此狀況抑制Drp1則會減少粒線體分裂,此外,Drp1也能調控細胞的自噬作用,並在養分匱乏時,影響細胞增殖。當Drp1被抑制時,會顯著地減少HBV蛋白生成、病毒的分泌、以及cccDNA的表現量。這些結果顯示:在肝癌細胞中,Drp1對於HBV的複製和病毒蛋白的生成扮演相當重要的角色。若瞭解Drp1參與HBV複製的調控機制,將有利於發展出新的治療方式,控制慢性B型肝炎感染的病人其肝癌的發生。
    Hepatocellular carcinoma (HCC) is a common cancer worldwide. Among many risk factors, hepatitis B virus (HBV) infection is the major risk for development of HCC. Mitochondria is a critical organelle for cellular functions, including ATP production, metabolism, calcium homeostasis, reactive oxygen species (ROS) signaling pathway and cell survival. Mitochondrial dynamics, including fusion and fission, is essential to maintain the number, biomass, morphology, and function of mitochondria. Previous studies have suggested HBx mutant and pre-S mutant large surface antigen (LHBs) play important roles in HCC. HBx have been demonstrated that promote aberrant mitochondrial dynamics. Researches focusing on the association between LHBs and mitochondria are limited. In this study, we aim to clarify the underlying mechanism and biological implication of LHBs on mitochondrial dynamics. We found that HBV or LHBs switched mitochondrial dynamic balanced towards fission through dynamic-related protein 1 (Drp1). Overexpression of a dominant-negative Drp1 suppressed mitochondria fission in hepatocytes. Besides, Drp1 also regulated autophagy and cell growth, in particularly under nutrient deprivation. Surprisingly, in the absence of Drp1, HBV production, viral secretion, and even cccDNA expression were all declined significantly. These results indicate that Drp1 plays an important role in HBV replication and virion production in hepatocytes. Understanding the mechanism of Drp1-involved HBV replication will be beneficial to develop a novel therapeutic strategy to control HBV replication in patients with chronic HBV infection.
    URI: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/86856
    Source: http://thesis.nthu.edu.tw/cgi-bin/gs/hugsweb.cgi?o=dnthucdr&i=sGH02102080529.id
    Appears in Collections:[分子與細胞生物研究所] 博碩士論文

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