臺灣博碩士論文加值系統

中文摘要
胃幽門螺旋桿菌居住在人類胃部，可使人產生慢性萎縮性胃炎、消化性潰瘍甚至後期造成胃癌。細胞毒素相關基A (CagA) 是此螺旋桿菌的一個致病因子，其與胃病有相關聯並且增加胃腺癌發生的風險。胃幽門螺旋桿菌的感染會調控貼附連接調控性蛋白質，使得細胞貼附不穩定以及人類胃上皮細胞的移動速度增加。近來發現窖蛋1 (caveolin-1) 的14號酪蛋白之磷酸化作用與細胞貼附所調節的訊息和細胞移動相關。但在胃幽門螺旋桿菌感染之後，窖蛋白1的磷酸化狀態並不清楚。所以，本論文著重在於研究胃幽門螺旋桿菌感染宿主細胞是否誘發窖蛋白1的14號酪胺酸處的磷酸化作用以及細胞毒素相關基因A是否與此事件有關。另外，本論文中也研究胃幽門螺旋桿菌誘發細胞外信號調節激酶 (ERK) 的磷酸化作用狀態。使用26695以及其細胞毒素相關基因A剔除的兩菌株來分析細胞毒素相關基因A對人類上皮細胞的窖蛋白1以及細胞外信號調節激酶的磷酸化作用之影響。宿主細胞的窖蛋白1以及細胞外信號調節激酶在胃幽門螺旋桿菌感染之後，發現這兩個蛋白質會被去磷酸化。而這些情形與細胞毒素相關基因A所調控的訊息無關。這些結果能給我們一個磷酸化的窖蛋白1包含在胃幽門螺旋桿菌所誘發的訊息傳遞途徑的初步證據。

Abstract
Helicobacter pylori (H. pylori) colonizes the human stomach and can cause gastric diseases such as chronic atrophic gastritis, peptic ulcers and even gastric cancer later in life. Cytotoxin-associated gene A (CagA), a virulence factor of H. pylori, associates with gastric disease and increases the risk of developing gastric adenocarcinoma. Infection of H. pylori regulates adherens junction regulatory proteins and results in destabilized epithelial cell adherence and increased rates of migration in human gastric epithelial cells. Recently, phosphorylation of caveolin-1 on tyrosine 14 is found to correlate with adhesion-dependent signaling and cell migration. However, the phosphorylation status of caveolin-1 after H. pylori infection is unclear. This study thus focuses on investigating whether phosphorylation of caveolin-1 on tyrosine 14 in host cells induced by H. pylori and whether CagA is involved in this event. Furthermore, the phosphorylation status of ERK induced by H. pylori infection was also investigated. H. pylori strain 26695 and isogenic cagA knockout strain were used for analyzing the effect of CagA on phosphorylation of caveolin-1 and phosphorylation of ERK in human epithelial cells. Caveolin-1 and ERK was found to be dephosphorylated in epithelial cells after H. pylori infection. These events were CagA-independent regulation of signaling. These results give us a preliminary evidence that phosphorylated caveolin-1 is involved in H. pylori-induced signal transduction pathway in epithelial cells.

Contents
Abstract V
中文摘要 VII
誌謝 VIII
Abbreviations IX
Contents X
List of Figures XI
Introduction 1
Materials and Methods 12
Results 21
Discussion 32
References 41
Appendix 59

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