Clostridium perfringens α-toxin activates the sphingomyelin metabolism system in sheep erythrocytes
Clostridium perfringens α-toxin activates the sphingomyelin metabolism system in sheep erythrocytes
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DOI：
10.1074/jbc.m307046200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Sakurai, J
中科院分区：
文献类型：
--
作者：
Ochi, S;Oda, M;Sakurai, J
产气荚膜梭菌α毒素通过激活甘油磷脂代谢诱导兔红细胞溶血。绵羊红细胞含有大量鞘磷脂（SM），但不含磷脂酰胆碱。我们研究了毒素诱导溶血与绵羊红细胞SM代谢系统的关系。α -毒素同时诱导溶血，降低SM水平，形成神经酰胺和鞘氨醇1-磷酸（S1P）。神经酰胺酶抑制剂n-油基乙醇胺抑制毒素诱导的溶血，使神经酰胺在毒素处理的细胞中积累。此外，从一种新型海洋细菌中分离出的DL-threo-dihydrosphingosine和B-5354c都是鞘氨醇激酶抑制剂，它们可以阻断毒素诱导的溶血和S1P的产生，并导致鞘氨醇的积累。这些观察结果表明，毒素诱导的SM代谢系统的激活与溶血密切相关。S1P增强了毒素诱导的皂素渗透红细胞溶血，但对完整细胞的溶血没有影响。用百日咳毒素预先孵育溶解的绵羊红细胞，可阻断α -毒素诱导的SM神经酰胺的形成。此外，经肉毒杆菌C3外泌酶处理的绵羊红细胞裂解物与α -毒素孵育可引起鞘氨醇的积累并抑制S1P的形成。这些观察结果表明，α -毒素诱导的绵羊红细胞溶血依赖于通过gtp结合蛋白激活SM代谢系统，特别是S1P的形成。
Clostridium perfringens alpha-toxin induces hemolysis of rabbit erythrocytes through the activation of glycerophospholipid metabolism. Sheep erythrocytes contain large amounts of sphingomyelin (SM) but not phosphatidylcholine. We investigated the relationship between the toxin-induced hemolysis and SM metabolic system in sheep erythrocytes. alpha-Toxin simultaneously induced hemolysis and a reduction in the levels of SM and formation of ceramide and sphingosine 1-phosphate (S1P). N-Oleoylethanolamine, a ceramidase inhibitor, inhibited the toxin-induced hemolysis and caused ceramide to accumulate in the toxin-treated cells. Furthermore, DL-threo-dihydrosphingosine and B-5354c, isolated from a novel marine bacterium, both sphingosine kinase inhibitors, blocked the toxin-induced hemolysis and production of S1P and caused sphingosine to accumulate. These observations suggest that the toxin-induced activation of the SM metabolic system is closely related to hemolysis. S1P potentiated the toxin-induced hemolysis of saponin-permeabilized erythrocytes but had no effect on that of intact cells. Preincubation of lysated sheep erythrocytes with pertussis toxin blocked the alpha-toxin-induced formation of ceramide from SM. In addition, incubation of C. botulinum C3 exoenzyme-treated lysates of sheep erythrocytes with alpha-toxin caused an accumulation of sphingosine and inhibition of the formation of S1P. These observations suggest that the alpha-toxin-induced hemolysis of sheep erythrocytes is dependent on the activation of the SM metabolic system through GTP-binding proteins, especially the formation of S1P.