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首页> 外文期刊>Journal of Epithelial Biology & Pharmacology >A Glucosylceramide Synthase Inhibitor Prevents the Cytotoxic Effects of Shiga Toxin-2 on Human Renal Tubular Epithelial Cells
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A Glucosylceramide Synthase Inhibitor Prevents the Cytotoxic Effects of Shiga Toxin-2 on Human Renal Tubular Epithelial Cells

机译：葡萄糖基神经酰胺合酶抑制剂可防止志贺毒素2对人肾小管上皮细胞的细胞毒作用

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Shiga toxin-2 binds to the globotriaosyl-ceramide receptor on the plasma membrane of target cells. The high level expression of this receptor in renal epithelial cells may account, at least in part, for acute renal failure observed in children with hemolytic uremic syndrome. The cytotoxic effect of Shiga toxin-2 was assayed on primary cultures of human renal tubular epithelial cells treated with a new specific inhibitor of glucosylceramide synthase (C-9), the ratelimiting first step in the glycosphingolipid biosynthetic pathway. The treatment of the cells with 1-5 μM C-9 for at least 24 h significantly neutralized the action of 1 ng/ml Shiga toxin-2 on cell viability. The expression levels of globotriaosylceramide significantly decreased when cells were incubated with 1 μM C-9 for 48 h. We propose here that prevention of globotriaosyl-ceramide synthesis by the C-9 could be a novel substrate inhibition therapy to neutralize Shiga toxin-2 action in renal epithelial cells.
机译：志贺毒素2与靶细胞质膜上的球果糖基神经酰胺受体结合。该受体在肾上皮细胞中的高水平表达可能至少部分解释了在溶血性尿毒症综合征患儿中观察到的急性肾衰竭。在使用新的特异性糖苷神经酰胺合酶抑制剂（C-9）处理的人肾小管上皮细胞的原代培养物中检测了志贺毒素2的细胞毒性作用，这是糖鞘脂生物合成途径中的限速第一步。用1-5μMC-9处理细胞至少24小时可显着中和1 ng / ml志贺毒素2对细胞活力的作用。当细胞与1μMC-9孵育48 h时，globotriaosylceramide的表达水平显着降低。我们在这里建议通过C-9预防球果糖基神经酰胺合成可能是一种中和志贺毒素2在肾上皮细胞中作用的新型底物抑制疗法。

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