title: Inhibitors of intravesicular acidification protect against Shiga toxin in a pH-independent manner.
abstract: Shiga toxin inhibits protein synthesis after being transported from the cell surface to endosomes and retrogradely through the Golgi apparatus to the endoplasmic reticulum (ER) and into the cytosol. In this study, we have abolished proton gradients across internal membranes in different ways and investigated the effect on the various transport steps of Shiga toxin. Although inhibitors of the proton pump such as bafilomycin A1 and concanamycin A as well as some ionophores and chloroquine all protect against Shiga toxin, they mediate protection by inhibiting different transport steps. For instance, chloroquine protects the cells, although the toxin is transported to the ER. Importantly, our data indicate that proton pump activity is required for efficient endosome-to-Golgi transport of Shiga toxin, although acidification as such does not seem to be required.
authors: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, 0379 Oslo, Norway.
authors: Anne Berit
authors: AB
authors: Dyve Lingelem
authors: Jonas
authors: J
authors: Bergan
authors: Kirsten
authors: K
authors: Sandvig
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D002738:Chloroquine / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects; D011992:Endosomes / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D022621:Shiga Toxin / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D018942:Macrolides; D022621:Shiga Toxin; C036978:concanamycin A; D002738:Chloroquine; C040929:bafilomycin A1; D009550:Nigericin