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Mechanism of Helicobacter pylonVacAintoxication

幽门螺杆菌疫苗中毒机制

基本信息

批准号：
16017280
负责人：
HIRAYAMA Toshiya
金额：
$ 9.6万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017280/
关键词：
Helicobacter pylori vacuolating cytotoxin VacA Mechanism of intoxication 阻害物質血清成分

项目摘要

Persistent infection with Helicobacter pylori causes chronic active gastritis, which predisposes the mucosa to peptic ulceration, and is believed to participate in the pathogenesis of gastric carcinoma and primary gastric lymphoma (i.e., mucosa-associated lymphoid tissue, or MALT type). Although H. pylori is a noninvasive bacterium that survives in the stomach mucosa, pathogenic strains of H. pylori produce and secrete a potent vacuolating cytotoxin, VacA.In this study, we examined and analyzed following two subjects : 1) Identification of the extracellular sequence of the receptor required for VacA binding and clarification of toxin internalization, and 2) Mechanism of cell death caused by VacA.Our results lead that1)These data define the region in the RPTPO extracellular domain critical for VacA binding, in particular, the sequence QTTQP at positions 747-751 with crucial threonines at positions 748 and 749, and are consisitent with a role for terminal sialic acids, possibly due to threonine glycosylation.VacA is concentrated in lipid rafts after binding to RPTP in non-lipid raft microdomains on AZ-521 cell surface. In addition, VacA-induced vacuolation as well as activation of p38 MAP kinase/ATF-2 (in submission).2) VacA acts through different signaling pathways to induce apoptosis via Bax activation, independent of vacuolation.

持续感染幽门螺杆菌可引起慢性活动性胃炎，使黏膜易发生消化性溃疡，被认为参与胃癌和原发性胃淋巴瘤（即粘膜相关淋巴组织，MALT型）的发病机制。虽然幽门螺杆菌是一种存活于胃粘膜的非侵入性细菌，但致病菌株幽门螺杆菌产生并分泌一种强效的空泡细胞毒素VacA。在本研究中，我们研究和分析了两个主题：1)VacA结合所需受体的细胞外序列的鉴定和毒素内化的澄清；2)VacA导致细胞死亡的机制。我们的研究结果表明：1)这些数据确定了RPTPO胞外结构域中对VacA结合至关重要的区域，特别是747-751位的QTTQP序列，748和749位的苏氨酸至关重要，并且与末端唾液酸的作用一致，可能是由于苏氨酸糖基化。VacA与AZ-521细胞表面非脂筏微域的RPTP结合后，在脂筏中集中。此外，vaca诱导的空泡形成以及p38 MAP激酶/ATF-2的激活（正在提交中）。2) VacA通过不同的信号通路通过Bax激活诱导细胞凋亡，不依赖于空泡化。

项目成果

期刊论文数量（45）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Cytotoxicity and recognition of receptor-like protein tyrosine phosphatases, RPTPa and RPTPO, by Helicobacter pylori m2VacA.

幽门螺杆菌 m2VacA 对受体样蛋白酪氨酸磷酸酶 RPTPa 和 RPTPO 的细胞毒性和识别。

DOI：
发表时间：
2005
期刊：
Cell Microbiol 7
影响因子：
0
作者：
De Guzman;B.B.;Hisatsune;J.;Nakayama;M.;Yahiro;K.;Wada;A.;Yamasaki;E.;Nishi;Y.;Yamazaki;S.;Azuma;T.;Ito;Y.;Ohtani;M.;van der Wijk;T.;den Hertog;J.;Moss;M.;Hirayama T.
通讯作者：
Hirayama T.

Gangliosides act as co-receptors for Salmonella enteritidis FliC and promote FliC induction of human β-defensin-2 expression in Caco-2 cells