Screening and purification of Shiga-like (Vero)toxin inhibitors

志贺样（Vero）毒素抑制剂的筛选和纯化

• 批准号: 09470073
• 负责人: NODA Masatoshi
• 金额: $ 2.56万
• 依托单位: Chiba Unibersity
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470073/
• 关键词: Shiga-like(Vero)toxin; virulence factor; O157 : H7; Vero cells; lethal toxicity; fluid accumulation; rabbit ileal loop; 白子蛋白; O157:H7; O157; Shiga-like toxin; 抗VT活性; 大黄; 桂皮

Shiga-like (Vero) toxin, a heterooligomeric protein composed of one A and five B subunit, is a major virulence factor produced by enterohemorrhagic Escherichia coli O157 : H7. The severe bloody diarrhea observed in E.coli 0157 patients is mediated by Shiga-like toxin- catalyzed cleavage of N-glycosidic bond of the adenosine at 4,324 from the 5'-terminal of the 28S ribosomal RNA of 60S ribosomal subunit in the target cells. We have investigated inhibitors of Shiga-like toxin, of natura1 origin, and found a candidate that inhibits the cytotoxicity of the toxin to Vero cells and a certain line of HeLa cells, lethal toxicity to mice and other small experimental animals, and bloody fluid accumulation in the rabbit ileal loop.

志贺样（Vero）毒素是由1个a亚基和5个B亚基组成的异聚蛋白，是肠出血性大肠杆菌O157: H7产生的主要毒力因子。大肠杆菌0157患者的严重血性腹泻是由志贺样毒素催化的靶细胞中60S核糖体亚基28S核糖体RNA 5′端4324处腺苷n-糖苷键的断裂介导的。我们已经研究了天然来源的志贺样毒素抑制剂，并发现了一种候选抑制剂，可以抑制毒素对Vero细胞和某些HeLa细胞的细胞毒性，对小鼠和其他小型实验动物的致死毒性，以及兔回肠袢中的血液积聚。

项目成果

Yamamoto S., Noda M., et al.: "A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity." Proc.Natl.Acad.Sci.84. 5267-5272 (1997)

Yamamoto S.、Noda M. 等人：“霍乱毒素的无毒突变体可引发 Th2 型反应，从而增强粘膜免疫。”

Yamaoka J., Noda M., et al.: "Loss of biological activity due to Glu→Arg mutation at residue 11 of the B subunit of cholera toxin." Microbial Pathogenesis. 23. 297-302 (1997)

Yamaoka J.、Noda M. 等人：“霍乱毒素 B 亚基残基 11 处的 Glu→Arg 突变导致生物活性丧失。”23. 297-302 (1997)

Kuwabara S., Noda M., et al.: "IgG-Anti-GM1 antibody is associated with reversible conduction failure and axonal degeneration in guillain-barre syndrome." Annals of Neurology. 44. 202-208 (1998)

Kuwabara S.、Noda M. 等人：“IgG-抗 GM1 抗体与格林巴利综合征的可逆性传导衰竭和轴突变性相关。”

Yamamoto,S., Noda,M.et al.: "A nontoxic mutant of cholera toxin elicits Th2-type responses for enhanced mucosal immunity." Proc.Natl.Acad.Sci.USA. 94. 5267-5272 (1997)

Yamamoto,S.、Noda,M.等人：“霍乱毒素的无毒突变体可引发 Th2 型反应，从而增强粘膜免疫。”

Suzuki K., Noda M., et al.: "The contribution of endogenous mono-ADP-ribosylation to kindling-induced epileptogenesis." Brain Research. 745. 109-113 (1997)

Suzuki K.、Noda M. 等人：“内源性单 ADP 核糖基化对引火诱发的癫痫发生的贡献。”