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标题：The relationship between the metabolism of sphingomyelin species and the hemolysis of sheep erythrocytes induced by Clostridium perfringens α-toxin
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作者：Masataka Oda ; Takayuki Matsuno ; Ryouta Shiihara 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：5
页码：1039-1047
DOI：10.1194/jlr.M700587-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Clostridium perfringens α-toxin induces the hemolysis of sheep erythrocytes by activating the metabolism of sphingomyelin (SM) via a GTP binding protein in membranes. α-Toxin stimulated the formation of 15- N -nervonoyl sphingosine (C_24:1-ceramide), which was identified by positive ion fast atom bombardment-MS and ¹H-NMR spectroscopy. C_24:1-ceramide stimulated the toxin-induced hemolysis of saponin-pretreated sheep erythrocytes and increased the production of sphingosine 1-phosphate (S1P) in the cells, but N -lignoceroyl sphingosine did not. These events elicited by the toxin in the presence of C_24:1-ceramide were significantly attenuated by treatment with dihydrosphingosine, a sphingosine kinase inhibitor. TLC showed that the level of C_24:1-ceramide was highest among the ceramides with an unsaturated bond in the fatty acyl chain in the detergent-resistant membranes (DRMs). The toxin specifically bound to DRMs rich in cholesterol, resulting in the hydrolysis of N -nervonoic sphingomyelin (C_24:1-SM) in DRMs. Treatment of the cells with pertussis toxin (PT) inhibited the α-toxin-induced formation of C_24:1-ceramide from C_24:1-SM in DRMs and hemolysis, indicating that endogenous sphingomyelinase, which hydrolyzes C_24:1-SM to C_24:1-ceramide, is controlled by PT-sensitive GTP binding protein in membranes. These results show that the toxin-induced metabolism of C_24:1-SM to S1P in DRMs plays an important role in the toxin-induced hemolysis of sheep erythrocytes.