Contribution of polyunsaturated fatty acids to Shiga toxin cytotoxicity in human renal tubular epithelium-derived cells.
Shiga toxin (Stx) produced by enterohemorrhagic Escherichia coli is a critical factor in the onset of hemolytic uremic syndrome. The current study was designed to assess whether n-3 and (or) n-6 polyunsaturated fatty acids (PUFA) act as a valuable adjunct to prevent the cell injury of renal tubule cells in the emergence of HUS. The target cells, ACHN cells derived from human tubule epithelium, were cultured with each PUFA, then exposed to Stx-1 or Stx-2. The rank order of potency of PUFA to inhibit the cell death caused by each toxin was as follows: EPA > AA = DHA >> LNA. There were dose-response relations in the efficacy of each PUFA. No prophylactic effect was found in the cultures with LA. Immunofluorescence assays revealed that both the expression of the toxin receptor on ACHN cells and binding between the toxin and cells were unaffected by the PUFA. These results suggest that EPA is the most efficacious PUFA against the renal tubule cell injury caused by Stx, which may be assigned to an alteration in the intracellular pathway leading to cell death.
Sasaki
Taku-Kemal
TK
Department of Nutritional Science, Faculty of Applied Biological Science, Tokyo University of Agriculture,Setagaya Ward, Japan. kemal-s@umin.ac.jp
Takita
Toshichika
T
D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004926:Escherichia coli / Q000472:pathogenicity; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage / Q000494:pharmacology*; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D022621:Shiga Toxin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity*; D022622:Shiga Toxin 1 / Q000633:toxicity; D022641:Shiga Toxin 2 / Q000633:toxicity; D014281:Trihexosylceramides / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005231:Fatty Acids, Unsaturated; D011956:Receptors, Cell Surface; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D014281:Trihexosylceramides; C018549:globotriaosylceramide; D022621:Shiga Toxin