| 研究生: |
李孟燕 Li, Meng-Yen |
|---|---|
| 論文名稱: |
坐骨神經傷害後WOX1蛋白在背根神經節的表現 upregulation of WW Domain Containing Oxidoreductase/WOX1 in the Injured Doresal Root Ganglion |
| 指導教授: |
王建平
Wang, Jiang-Ping |
| 學位類別: |
碩士 Master |
| 系所名稱: |
生物科學與科技學院 - 生命科學系 Department of Life Sciences |
| 論文出版年: | 2005 |
| 畢業學年度: | 93 |
| 語文別: | 英文 |
| 論文頁數: | 73 |
| 中文關鍵詞: | 背根神經節 、WOX1 、坐骨神經傷害 |
| 外文關鍵詞: | ATF3, WOX1, Dorsal Root Ganglion |
| 相關次數: | 點閱:165 下載:5 |
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中文摘要
人類WWOX 基因是位於容易斷裂的第十六對染色體長臂23.3-24.1的位置,在多種的癌症中常發現此斷裂基因造成異質染色體的缺失,因此WWOX基因被定義為腫瘤抑制基因。WWOX基因所轉譯出來的WOX1蛋白是一種細胞凋亡前蛋白,當細胞受到刺激WOX1會經由胺基酸端的酪氨酸33磷酸化而成為一種活化態的p-WOX1,並進一步移位到細胞核與p53相互作用進而使細胞走向凋亡,另一方面活化態的WOX1也會移位到粒線體。本實驗利用in vivo 胞外研究方法探討WOX1在神經系統的角色,我們觀察坐骨神經傷害後WOX1在背根神經節與脊髓的表現。以免疫組織化學法觀察第四/五節的背根神經節,在坐骨神經傷害6小時後,在傷害的同側WOX1明顯有移位到細胞核的情況;而對側神經節或控制組中,WOX1多存在細胞質,只有少部分細胞核有WOX1的表現,脊髓背角感覺神經元及腹角運動神經元則沒發現WOX1的改變。此外,以電子顯微鏡免疫金與免疫螢光染色的方法發現,在坐骨神經傷害後,WOX1會與一些Immediate-early genes (IEGs) 如: activation transcription factor 3 (ATF3)、c-Jun相互作用並同時表現在細胞核內。因此初步認為WOX1除了是一種細胞凋前蛋白,在神經系統傷害初期也可能具有調控其他基因表現的功能。
Abstract
Human WWOX gene is located on a chromosomal fragile site ch16q23.3-24.1.Hight frequency of loss of heterozygosity (LOH) of this gene has been shown in multiple cancer. The WWOX gene encodes a putative tumor suppressor WW domain-containing oxidoreductase WOX1 (also known as WWOX or FOR2). WOX1 is a proapoptotic protein. Stress stimuli activate WOX1 via tyrosine 33 (Try33) phosphorylation, resulting the its complex formation with p53 and translocation to nuclear mediate apoptosis. Here, we investigate the potential role of WOX1 in L4/5 dorsal root ganglia (DRG) and spinal cord and its interaction with other transcription factors in vivo following sciatic nerve transaction. By immunocytochemistry, nuclear translocation of WOX1 was observed in DRG neurons 6 hours ipsilaterally to axotomy. WOX1 upregulation was also expressed in the cytoplasm of DRG at the contrlateral side as comparea normal control animal, but low levels in the nuclei, WOX1 expression did not change in the spinal cord. By using electron microscopy, we showed that WOX1 colocalized with immediate-early genes (IEGs) such as activation transcription factor 3 (ATF3) and c-Jun. These findings suggest that WOX1 might be involved in not only apoptosis but also the regulation of gene expression in the peripheral nerve system.
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