岩藻醣水解酶於幽門螺旋桿菌感染胃癌細胞扮演之角色

全球約有50%的人口感染幽門螺旋桿菌；研究顯示，這個病原菌與胃炎、十二指腸潰瘍與胃癌的形成，有直接的相關性。幽門螺旋桿菌與宿主細胞間如何傳達訊息而互相影響？再者，這種交互作用的機制，是否對於不同胃部疾病的形成有關？這些問題到目前為止還不是很清楚。利用對含有岩藻醣的複合醣做螢光標示，我們發現幽門螺旋桿菌可以從宿主細胞攝入岩藻醣，在共同培養幽門螺旋桿菌與宿主細胞的條件下（以幽門螺旋桿菌去感染宿主細胞），宿主細胞會分泌出第二型岩藻醣水解酶到共同培養液中。利用RNA干擾技術降低宿主細胞第二型岩藻醣水解酶的表現，可以降低CagA（幽門螺旋桿菌的一種毒性分子）轉移到宿主細胞內的比例。因此，第二型岩藻醣水解酶的存在可能與幽門螺旋桿菌附著到宿主細胞表面的能力有關，尤其對從十二指腸潰瘍與胃癌病人取出的幽門螺旋桿菌株有所影響。另外，第二型岩藻醣水解酶的表現，可以增加幽門螺旋桿菌路易士X抗原的形成，此類醣分子除了加強對宿主細胞的附著能力，還可以作為偽裝胃壁細胞表面的醣分子種類，藉此躲避宿主免疫系統的攻擊。這些發現，不只證實了宿主第二型岩藻醣水解酶對於幽門螺旋桿菌的附著、生長與致病的能力有關，也說明了此酵素對於幽門螺旋桿菌所導致的相關疾病，可以作為一個臨床診斷與治療潛力的標的物。

關鍵字

幽門螺旋桿菌；岩藻醣；岩藻醣水解酶毒性分子；胃部疾病

並列摘要

Infecting about one-half of the global human population, Helicobacter pylori is well established as the primary cause of gastritis, duodenal ulcer and gastric cancer. Currently there is no clear information regarding if and how host cells interact with H. pylori and if such interactions are dependent on the type of gastric disease. Using fluorescently labeled fucose-containing glycoconjugates, we provide the first evidence observing both the uptake of L-fucose from gastric cancer cells to H. pylori and that human α-L-fucosidase 2 (FUCA2) is secreted only under co-culture conditions (i.e., host cells infected with H. pylori). Upon depletion of FUCA2 by RNA interference and detection of translocated CagA (a virulence factor of H. pylori) in host cells, FUCA2 was found to be essential for H. pylori adhesion, in particular to the gastric cancer- and duodenal ulcer-specific strains. Additionally FUCA2 was shown to significantly enhance the expression of Lewis x antigen in H. pylori, which is critical for the bacterial cell adhesion in the pathogenesis and defense strategy to escape from host surveillance. These findings not only demonstrate an important connection between FUCA2 and the adhesion, growth and pathogenicity of H. pylori, but also support the idea that FUCA2 is a potential target for clinical diagnosis and therapeutic intervention of H. pylori-related diseases.

並列關鍵字

Helicobacter pylori ； fucose ； fucosidase ； virulence ； gastric disease

參考文獻

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3. Sipponen P, Hyvarinen H (1993) Role of Helicobacter pylori in the pathogenesis of gastritis, peptic ulcer and gastric cancer. Scand. J. Gastroenterol. Suppl. 196:3–6.

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岩藻醣水解酶於幽門螺旋桿菌感染胃癌細胞扮演之角色

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