Thioredoxin reductase inhibitor auranofin prevents membrane transport of diphtheria toxin into the cytosol and protects human cells from intoxication.
During cellular uptake, diphtheria toxin delivers its catalytic domain DTA from acidified endosomes into the cytosol, which requires reduction of the disulfide linking DTA to the transport domain. In vitro, thioredoxin reduces this disulfide and thioredoxin reductase (TrxR) is part of a cytosolic complex facilitating DTA-translocation. We found that the TrxR-specific inhibitor auranofin prevented DTA delivery into the cytosol and intoxication of HeLa cells with diphtheria toxin, offering perspectives for novel pharmacological strategies against diphtheria.
['Schnell|Leonie|L|', 'Dmochewitz-Kück|Lydia|L|', 'Feigl|Peter|P|', 'Montecucco|Cesare|C|', 'Barth|Holger|H|']
D001310:Auranofin D001692:Biological Transport D003600:Cytosol D004167:Diphtheria Toxin D006367:HeLa Cells D006801:Humans D006863:Hydrogen-Ion Concentration D020011:Protective Agents D013880:Thioredoxin-Disulfide Reductase
Thioredoxin reductase Auranofin Diphtheria toxin Cellular uptake Endosome Membrane translocation