跳到主要內容

臺灣博碩士論文加值系統

(3.235.174.99) 您好!臺灣時間:2021/07/24 17:56
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果 :::

詳目顯示

: 
twitterline
研究生:陳茵芝
研究生(外文):Yin-chih Chen
論文名稱:spike在T細胞活化與凋亡所扮演的角色
論文名稱(外文):The role of spike in T cell activation and apoptosis
指導教授:賴明宗賴明宗引用關係
指導教授(外文):Ming-zong Lai
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:微生物及免疫學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:54
中文關鍵詞:BH3-only 蛋白質T 細胞活化細胞凋亡內質網壓力
外文關鍵詞:BH3-only proteinT cell activationapoptosisER stressspike
相關次數:
  • 被引用被引用:0
  • 點閱點閱:160
  • 評分評分:
  • 下載下載:21
  • 收藏至我的研究室書目清單書目收藏:0
Spike 是位於內質網的 BH3-only 蛋白質。Spike 被認為會與 Bap31 結合,參與在 Fas-mediated 細胞死亡,並且活化 caspase-3。然而 spike 、Bap31 或 A4 是否參與在 T 細胞活化的訊息路徑上,仍未有清楚的定論。本篇論文利用反轉錄病毒感染 T 細胞的方式,將 spike 送入 T 細胞中表現,並且利用 siRNA 和 antisense oligo 降低 T 細胞中 spike 表現,以研究 spike 在 T 細胞活化、 Fas 與粒線體主導的細胞凋亡與內質網壓力引起的細胞凋亡中所扮演的角色。
在探討 T 細胞活化方面,大量表現 spike 對 DO11.10 細胞活化後 IL-2 產生與 Jurkat 細胞活化時鈣離子進入細胞質沒有影響。降低 EL4 細胞中spike 表現量亦不影響活化後 IL-2 產生。在探討死亡配體引起 T 細胞凋亡方面,大量表現 spike 對 Jurkat 細胞 Fas-mediated 細胞凋亡沒有影響。對 DO11.10 細胞 Fas-mediated AICD (Activation induced cell death ) 亦無影響。在探討 mitochondria-mediated 細胞凋亡方面,大量表現 spike 對 DO11.10 細胞經 etoposide 與 cisplatin 所誘發的細胞死亡沒有影響。在 ER stress-induced 細胞凋亡方面,大量表現 spike 對 DO11.10 細胞經 DTT 與 BFA 所誘發的細胞死亡沒有影響。相反的,對 DO11.10 細胞經 tunicamycin 誘發的細胞死亡會受到抑制。Spike 的大量表現不影響 DO11.10 經 tunicamycin 所誘導 Grp78/Bip 表現量,但是 PERK 磷酸化的時間點被延後。我們也發現 tunicamycin 所引起的細胞死亡,並沒有因為以 siRNA 降低 spike 表現量而受到影響。因此 spike 沒有參與 T 細胞活化、Fas-induced 細胞凋亡或是mitochondria-mediated 細胞死亡。Spike亦無參與 DTT 與 BFA 的誘發死亡。Spike 是如何選擇性的參與 tunicamycin-triggered 細胞凋亡與其參與的機制需要進一步的實驗去探討
Spike is a BH3-only proteins located at ER. Spike has been suggested to bind Bap31, participate in Fas-mediated cell death, and induced caspase-3 activation. However spike, Bap31 or A4 is involved in T cell activation remains elusive. In this study the exact role of spike in T cell activation, Fas- and mitochondria- initiated apoptosis and ER stress-induced cell death was studied by overexpression of spike in T cells through retroviral infection, and by downregulation of spike through antisense oligo and siRNA.
For T cell activation, spike overexpression did not affect IL-2 production in DO11.10 T cells and calcium influx in Jurkat cells. Downregulation of spike expression by antisense did not affect IL-2 production in DO11.10 cells. For death receptor-mediated apoptosis, overexpression of spike did not influence Fas-induced apoptosis in Jurkat cells, nor was Fas-mediated AICD in DO11.10 cells affected. For mitochondria-mediated cell death, overexpression of spike did not affect etoposide- and cisplatin-triggered apoptosis in DO11.10 cells. For ER stress-induced cell death, DTT and BFA-induced cell death was unaffected in DO11.10 cells overexpressing spike. In contrast, tunicamycin-induced cell death was inhibited in spike-expressing DO11.10 cells. The induction of Grp78/Bip by tunicamycin was normal in DO11.10 cells overexpressing spike, but the PERK phosphorylation was attenuated. We also found that tunicamycin-induced cell death was unaffected by knock down endogenous spike with siRNA. Therefore, spike is not involved in T cell activation, Fas-induced apoptosis, or mitochondria-mediated cell death. Spike is also not required for BFA- and DTT- triggered cell death, yet spike partially inhibit tunicamycin-induced apoptosis. Further studies are required to delineate the molecular mechanism how spike selectively prevent tunicamycin-triggered apoptosis.
Berridge MJ. (2002). The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium. 32, 235-249.
Bertolotti A, Zhang Y, Hendershot LM, Harding HP, Ron D. (2000). Dynamic interaction of BiP and ER stress transducers in the unfolded-protein response. Nat Cell Biol. 2, 326-332.
Bouillet P, Strasser A. (2002). BH3-only proteins - evolutionarily conserved proapoptotic Bcl-2 family members essential for initiating programmed cell death. J Cell Sci. 115, 1567-1574
Breckenridge DG, Germain M, Mathai JP, Nguyen M, Shore GC. (2003). Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene. 22, 8608-8618
Breckenridge DG, Nguyen M, Kuppig S, Reth M, Shore GC. (2002). The procaspase-8 isoform, procaspase-8L, recruited to the BAP31 complex at the endoplasmic reticulum. Proc Natl Acad Sci U S A. 99, 4331-4336
Breckenridge DG, Stojanovic M, Marcellus RC, Shore GC. (2003). Caspase cleavage product of BAP31 induces mitochondrial fission through endoplasmic reticulum calcium signals, enhancing cytochrome c release to the cytosol. J Cell Biol. 160, 1115-1127.
Cory S, Huang DC, Adams JM. (2003). The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 22, 8590-8607.
Fujita E, Kouroku Y, Jimbo A, Isoai A, Maruyama K, Momoi T. (2002). Caspase-12 processing and fragment translocation into nuclei of tunicamycin-treated cells. Cell Death Differ. 9, 1108-1114.
Hong M, Li M, Mao C, Lee AS. (2004). Endoplasmic reticulum stress triggers an acute proteasome-dependent degradation of ATF6. J Cell Biochem. 92, 723-732.
Huang DC, Strasser A. (2000) BH3-Only proteins-essential initiators of apoptotic cell death. . Cell. 103, 839-842.
Iwawaki T, Hosoda A, Okuda T, Kamigori Y, Nomura-Furuwatari C, Kimata Y, Tsuru A, Kohno K. (2001). Translational control by the ER transmembrane kinase/ribonuclease IRE1 under ER stress. Nat Cell Biol. 3, 158-64.
Kalai M, Lamkanfi M, Denecker G, Boogmans M, Lippens S, Meeus A, Declercq W, Vandenabeele P. (2003). Regulation of the expression and processing of caspase-12. J Cell Biol. 162, 457-467.
Lamkanfi M, Kalai M, Vandenabeele P. (2004). Caspase-12: an
overview. Cell Death Differ. 11, 356-358.
Maag RS, Hicks SW, Machamer CE. (2003). Death from within:
apoptosis and the secretory pathway. Curr Opin Cell Biol. 15, 456-461.
Marsden VS, Strasser A. (2003) Control of apoptosis in the immune system: Bcl-2, BH3-only proteins and more. . Annu Rev Immunol. 21, 71-105
Mouw G, Zechel JL, Gamboa J, Lust WD, Selman WR, Ratcheson RA. (2003). Activation of caspase-12, an endoplasmic reticulum resident caspase, after permanent focal ischemia in rat. Neuroreport. 14, 183-186.
Mund T, Gewies A, Schoenfeld N, Bauer MK, Grimm S. (2003). Spike, a novel BH3-only protein, regulates apoptosis at the endoplasmic reticulum. FASEB J. 17, 696-698
Nakagawa T, Yuan J. (2000). Cross-talk between two cysteine protease families. Activation of caspase-12 by calpain in apoptosis. J Cell Biol. 150, 887-894.
Ng FW, Nguyen M, Kwan T, Branton PE, Nicholson DW, Cromlish JA, Shore GC. (1997). p28 Bap31, a Bcl-2/Bcl-XL- and procaspase-8-associated protein in the endoplasmic reticulum. J Cell Biol. 139, 327-338.
Ng FW, Shore GC. (1998) Bcl-XL cooperatively associates with the Bap31 complex in the endoplasmic reticulum, dependent on procaspase-8 and Ced-4 adaptor. J Biol Chem. 273, 3140-3143.
Nguyen M, Breckenridge DG, Ducret A, Shore GC. (2000). Caspase-resistant BAP31 inhibits fas-mediated apoptotic membrane fragmentation and release of cytochrome c from mitochondria. Mol Cell Biol. 20, 6731-6740.
Oakes SA, Opferman JT, Pozzan T, Korsmeyer SJ, Scorrano L. (2003). Regulation of endoplasmic reticulum Ca2+ dynamics by proapoptotic BCL-2 family members. Biochem Pharmacol. 66, 1335-1340.
Orrenius S, Zhivotovsky B, Nicotera P. (2003). Regulation of cell death: the calcium-apoptosis link. Nat Rev Mol Cell Biol. 4, 552-565.
Oyadomari S, Araki E, Mori M. (2002). Endoplasmic reticulum
stress-mediated apoptosis in pancreatic beta-cells. Apoptosis. 7, 335-345.
Oyadomari S, Mori M. (2004). Roles of CHOP/GADD153 in
endoplasmic reticulum stress. Cell Death Differ. 11, 381-389.
Rao RV, Peel A, Logvinova A, del Rio G, Hermel E, Yokota T, Goldsmith PC, Ellerby LM, Ellerby HM, Bredesen DE. (2002). Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 514, 122-128.
Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS. (2003). Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem. 278,20915-20924.
Rudner J, Jendrossek V, Belka C. (2002). New insights in the role of Bcl-2 Bcl-2 and the endoplasmic reticulum. Apoptosis. 7, 441-447
Shibata M, Hattori H, Sasaki T, Gotoh J, Hamada J, Fukuuchi Y. (2003). Activation of caspase-12 by endoplasmic reticulum stress induced by transient middle cerebral artery occlusion in mice. Neuroscience. 118, 491-499
Thomenius MJ, Distelhorst CW. (2003). Bcl-2 on the endoplasmic reticulum: protecting the mitochondria from a distance. J Cell Sci. 116, 4493-4499.
Wang B, Nguyen M, Breckenridge DG, Stojanovic M, Clemons PA, Kuppig S, Shore GC. (2003). Uncleaved BAP31 in association with A4 protein at the endoplasmic reticulum is an inhibitor of Fas-initiated release of cytochrome c from mitochondria. J Biol Chem. 18, 14461- 14468
Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M. (2001). Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem. 276, 13935-13940.
Zong WX, Li C, Hatzivassiliou G, Lindsten T, Yu QC, Yuan J, Thompson CB. (2003). Bax and Bak can localize to the endoplasmic reticulum to initiate apoptosis. J Cell Biol. 162, 59-69.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊