LDL-dependent cytotoxicity of Shiga toxin in the cells devoid of Gb3

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The present investigation was aimed to clarify the mechanism by which Shiga toxin (Stx) would express its biological action in the cells devoid of Gb3. Monohexosylceramide (Lc2Cer), Gb3Cer, and Gb4Cer were found in both intestinal and plasma glycosphingolipid (GSL). Plasma GSLs exhibited heterogeneity of free fatty acids in their lipid ceramide anchors. Synthesized GSL-Stx2 liposome bound to LDL and VLDL with high affinity. GSL-Stx2 liposomes with the high affinity have the relative composition of C24:0/C24:1 as Gb3Cer moiety, accounting for their heterogeneity. GSL-Stx2 liposomes capable of binding to LDL were easily taken-up by the cells devoid of Gb3 receptors.These results indicated a new mechanism of the expression of Stx cytotoxicity to the cells, devoid of Gb3 receptors: the complex of GSL-Stx-LDL can be taken-up through LDL receptors before internalization.