Submitted to: Toxicologist
Publication Type: Abstract only
Publication Acceptance Date: 1/15/2001
Publication Date: 3/1/2001
Citation: Interpretive Summary:
Technical Abstract: Escherichia coli strains producing Shiga like toxins (Stx 1 and 2) colonize in the intestine in humans and the toxins pass from the intestinal tract lumen to the blood. The toxins translocated across the intestinal epithelial cells are associated with systemic diseases, such as HUS syndrome. It is well known that Stx 1 binds the neutral glycosphingolipid, globotriaosylceramide (Gb3), on the surface of epithelial cells. Once internalized it inhibits protein synthesis. However, the role of globosides on translocation across the intestinal epithelial cells is unclear. The purpose of this study was to elucidate the effect of inhibitors of glycosphingolipid biosynthesis on translocation of Stx 1 using the human intestinal cell line (Caco-2). Fumonisin B1 (FB1) and PDMP decreased the contents of glycosphingolipid, Gb3 on the surface of Caco-2 cells but they had no effect on the barrier function as assessed by measuring transepithelial electrical resistance. 125I-Stx 1 bound the surface of FB1-treated cells the same as that of control cells. Nonetheless, FB1 and PDMP treatment increased Stx 1 translocation and completely blocked the Stx 1-induced protein synthesis inhibition. These results demonstrate that Stx 1 binding and increased translocation in Caco-2 cells treated with FB1 is not Gb3 dependent. However, inhibition of glycosphingolipid biosynthesis modulates both translocation and STX-1-induced protein synthesis inhibition independent of Gb3 expression.