Protection against Shiga Toxins.
Shiga toxins consist of an A-moiety and five B-moieties able to bind the neutral glycosphingolipid globotriaosylceramide (Gb3) on the cell surface. To intoxicate cells efficiently, the toxin A-moiety has to be cleaved by furin and transported retrogradely to the Golgi apparatus and to the endoplasmic reticulum. The enzymatically active part of the A-moiety is then translocated to the cytosol, where it inhibits protein synthesis and in some cell types induces apoptosis. Protection of cells can be provided either by inhibiting binding of the toxin to cells or by interfering with any of the subsequent steps required for its toxic effect. In this article we provide a brief overview of the interaction of Shiga toxins with cells, describe some compounds and conditions found to protect cells against Shiga toxins, and discuss whether they might also provide protection in animals and humans.
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway. simona.kavaliauskiene@rr-research.no.|Center for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, N-0379 Oslo, Norway. simona.kavaliauskiene@rr-research.no.
Simona
S
Kavaliauskiene
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway. Anne.Berit.Dyve@rr-research.no.|Center for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, N-0379 Oslo, Norway. Anne.Berit.Dyve@rr-research.no.
Anne Berit
AB
Dyve Lingelem
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway. Tore.Skotland@rr-research.no.|Center for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, N-0379 Oslo, Norway. Tore.Skotland@rr-research.no.
Tore
T
Skotland
Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, N-0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.|Center for Cancer Biomedicine, Faculty of Medicine, Oslo University Hospital, N-0379 Oslo, Norway. kirsten.sandvig@ibv.uio.no.|Department of Biosciences, University of Oslo, N-0316 Oslo, Norway. kirsten.sandvig@ibv.uio.no.
Kirsten
K
Sandvig
D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D017209:Apoptosis; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D006463:Hemolytic-Uremic Syndrome / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D054884:Host-Pathogen Interactions; D006801:Humans; D014176:Protein Biosynthesis; D011487:Protein Conformation; D021381:Protein Transport; D022603:Shiga Toxins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D054323:Shiga-Toxigenic Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D012762:Shigella dysenteriae / Q000187:drug effects* / Q000378:metabolism / Q000472:pathogenicity; D013329:Structure-Activity Relationship; D014281:Trihexosylceramides / Q000378:metabolism
D000931:Antidotes; D001426:Bacterial Proteins; D022603:Shiga Toxins; D014281:Trihexosylceramides; C018549:globotriaosylceramide
Mn2+; Shiga toxin; Stx1; Stx2; chloroquine; fluorodeoxyglucose; hemolytic uremic syndrome; inhibitors