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希加毒素诱导的ATP释放的细胞信号通路

Karl Johansson¹, Ida Arvidsson¹, Markus Wendler¹

¹Department of Pediatrics, Clinical Sciences Lund, Lund University, Lund, Sweden.

Frontiers in cellular and infection microbiology

|March 11, 2026

概括

石毒素 (Stx) 通过激活涉及G蛋白,PI3K和IP3R的信号通路,触发ATP释放和细胞死亡. 抑制这种途径可以防止Stx诱导的亡,并改变小鼠的PIP2表达.

科学领域:

微生物学微生物学
细胞生物学细胞生物学
毒理学毒理学毒理学

背景情况:

来自肠道出血大肠杆菌的Shiga毒素 (Stx) 是一个关键的毒性因子.
Stx会引起胃肠炎和血液溶解尿素综合征.
Stx诱导ATP释放,阻断纯能P2X受体可以降低其细胞毒性.

研究的目的:

研究Stx诱导的ATP释放之前的细胞内信号事件.
阐明特定信号分子在Stx细胞毒性中的作用.
确定抑制关键信号通路对STX效应的影响.

主要方法:

使用了G蛋白结合受体 (百日咳毒素),PI3K (丁胺,阿尔佩利西布),脂酶C (曼诺利德) 和IP3R (2-APB) 的抑制剂.
操纵细胞内和细胞外水平.
静止了内醇1,4,5-三酸盐受体 (IP₃R),并通过caspase 3/7激活评估了亡.
给小鼠 Stx2,与或没有 alpelisib 前期治疗,并分析脏 PIP2 表达.

主要成果:

Stx1诱导的ATP释放被Gi/o G蛋白结合受体,PI3K,脂酶C和IP₃R的抑制剂以及耗耗阻断.
IP₃R阻断或沉默受保护的HeLa细胞,防止Stx1和Stx2诱导的亡.
在小鼠中,Stx2的挑战导致了明显的质PIP2染色,PI3K抑制剂alpelisib减少了这种染色.

结论:

Stx与HeLa细胞的相互作用启动了涉及G蛋白,PI3K,脂酶C和IP₃R的信号级联,最终导致ATP释放和细胞毒性.
PI3K通路和IP₃R是Stx诱导的细胞损伤的关键调解者.
向PI3K通路,正如alpelisib所示,会影响Stx2挑战小鼠中的PIP2表达.

关键词:

这就是ATPATPATP ATP.这是一种G蛋白质蛋白质,G蛋白质蛋白质.石加毒素是一种毒素.全球三基胺.伊诺西 1,4,5-三酸盐受体的受体酸 4,5-双酸盐是一种酸.

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