Polyunsaturated fatty acids regulate Shiga toxin transport.
Shiga toxin (Stx) is internalized by receptor-mediated endocytosis and transported retrogradely to the endoplasmic reticulum from where the enzymatically active part of the toxin is translocated to the cytosol. In this study, we have investigated the effect of polyunsaturated fatty acids (PUFA) on intoxication and retrograde transport of Stx. In HEp-2 cells, PUFA treatment inhibited Stx intoxication by a factor of 10. Moreover, both Stx internalization and endosome-to-Golgi transport were reduced by PUFA and these reductions can together explain the reduced toxicity. Also cholera toxin internalization was reduced by PUFA treatment. Finally, ricin and Pseudomonas exotoxin 1 cytotoxicity were not reduced by PUFA, demonstrating that PUFA do not cause a general block in retrograde transport to the endoplasmic reticulum. In conclusion, these results clearly demonstrate the importance of PUFA for Stx and cholera toxin trafficking.
Spilsberg
Bjørn
B
Department of Biochemistry, Centre for Cancer Biomedicine, Institute for Cancer Research, Faculty Division The Norwegian Radium Hospital, University of Oslo, Montebello, N-0310 Oslo, Norway.
Llorente
Alicia
A
Sandvig
Kirsten
K
D001693:Biological Transport, Active; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000378:metabolism; D004041:Dietary Fats / Q000494:pharmacology*; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D005098:Exotoxins / Q000633:toxicity; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D021381:Protein Transport; D011549:Pseudomonas / Q000378:metabolism; D012276:Ricin / Q000378:metabolism / Q000633:toxicity; D022621:Shiga Toxin / Q000378:metabolism* / Q000633:toxicity; D014168:Transferrin / Q000378:metabolism
D004041:Dietary Fats; D005098:Exotoxins; D005231:Fatty Acids, Unsaturated; D014168:Transferrin; D022621:Shiga Toxin; D012276:Ricin; D002772:Cholera Toxin