Analysis on multifunctional receptors for Helicobacter pylori VacA

幽门螺杆菌VacA多功能受体分析

• 批准号: 22390084
• 负责人: HIRAYAMA Toshiya
• 金额: $ 12.06万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22390084/
• 关键词: ヘリコバクター・ピロリ; VacA; 細菌毒素; 細菌毒素受容体; VacA受容体; 毒性発現; 毒素作用; 毒素受容体; ピロリ菌

The pleiotropic effects of vacuolating cytotoxin (VacA) produced by Helicobacter pylori appear to result from activation of different signal transduction pathways through binding to several epithelial cell receptors, e.g., receptor protein tyrosine phosphatase (RPTP) β and α, and fibronectin. Here we purified from AZ-521 cells, a human gastric epithelial ell line, a surface membrane protein, p500, which binds VacA, and identified it as low-density lipoprotein receptor-related protein-1 (LRP1). LRP1 binding of VacA was shown to be specifically responsible for VacA-induced autophagy and apoptosis, but not activation of the Wnt/β-catenin signaling pathway. Similar to RPTPα and RPTP β, LRP1 mediates VacA internalization in AZ-521 cells, but in contrast to RPTPα and RPTP β, LRP1 targeted downstream pathways leading to autophagy and apoptosis. VacA-induced autophagy via LRP1 binding precedes apoptosis suggesting that an excessive autophagic activity can also lead to cell death. This is the first study to provide evidence that LRP1 mediates autophagy.

幽门螺杆菌产生的空泡细胞毒素（VacA）的多效性似乎是由于通过与几种上皮细胞受体结合激活不同的信号转导途径，例如受体蛋白酪氨酸磷酸酶(RPTP) β和α，以及纤维连接蛋白。我们从人胃上皮细胞系AZ-521细胞中纯化了一种结合VacA的表面膜蛋白p500，并鉴定其为低密度脂蛋白受体相关蛋白-1 （LRP1）。LRP1结合VacA被证明特异地负责VacA诱导的自噬和凋亡，但不激活Wnt/β-catenin信号通路。与RPTPα和RPTP β类似，LRP1介导AZ-521细胞中VacA的内化，但与RPTPα和RPTP β相反，LRP1靶向下游途径导致自噬和凋亡。通过LRP1结合的vaca诱导的自噬先于细胞凋亡，这表明过度的自噬活性也可导致细胞死亡。这是首次提供证据证明LRP1介导自噬。

项目成果

Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells

• DOI: 10.1242/dmm.004879
• 发表时间: 2010-09-01
• 期刊: DISEASE MODELS & MECHANISMS
• 影响因子: 4.3
• 作者: Akada, Junko K.;Aoki, Hiroki;Nakamura, Kazuyuki
• 通讯作者: Nakamura, Kazuyuki

Pleiotropic action of VacA toxin of Helicobacter pylori

幽门螺杆菌 VacA 毒素的多效作用

• 发表时间: 2012
• 作者: 原英樹;Adaobi Igwilo;土屋晃介;山本武司; Eduardo Hernandez-Cuellar ;河村伊久雄;光山正雄;Mulyanto;兒玉 雅明;Toshiya Hirayama
• 通讯作者: Toshiya Hirayama

MicroRNA signatures in Helicobacter pylori-infected gastric mucosa

• DOI: 10.1002/ijc.25348
• 发表时间: 2011-01-15
• 期刊: INTERNATIONAL JOURNAL OF CANCER
• 影响因子: 6.4
• 作者: Matsushima, Kayoko;Isomoto, Hajime;Kohno, Shigeru
• 通讯作者: Kohno, Shigeru

Evalution of the Function of Stn produced by salmonella.

沙门氏菌产生的 Stn 的功能评价。

• 发表时间: 2012
• 作者: 酒井俊佑;河村伊久雄;土屋晃介;光山正雄;Okamoto H;Ahmed M.Hammad;Masayuki Nakano,Eiki Yamasaki,Takaaki Shimamoto,Akira Takahashi,Hisao Kurazono,Toshiya Hirayama
• 通讯作者: Masayuki Nakano,Eiki Yamasaki,Takaaki Shimamoto,Akira Takahashi,Hisao Kurazono,Toshiya Hirayama

Clinical significance of microRNAs in H.pylori-associated gastritis.

microRNA 在 H.pylori 相关性胃炎中的临床意义。

• 发表时间: 2011
• 作者: Kayoko Matsushima;Hajime Isomoto;Shigeru Kohno ,Yuko Akazawa ,Naoyuki Yamaguchi;Ken Ohnita;Tatsuki Ichikawa ,Fuminao Takeshima;Kazuhiko Nakano;Toshiya Hirayama
• 通讯作者: Toshiya Hirayama