Thioredoxin reductase inhibitor auranofin prevents membrane transport of diphtheria toxin into the cytosol and protects human cells from intoxication.

Abstract

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.

• Authors: Leonie Schnell, Lydia Dmochewitz-Kück, Peter Feigl, Cesare Montecucco, Holger Barth
• Journal: Toxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 116 Pg. 23-8 (Jun 15 2016) ISSN: 1879-3150 [Electronic] England
• PMID: 25911959 (Publication Type: Journal Article)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Diphtheria Toxin
• Protective Agents
• Auranofin
• Thioredoxin-Disulfide Reductase

Topics

• Auranofin (pharmacology)
• Biological Transport (drug effects)
• Cytosol (metabolism)
• Diphtheria Toxin (metabolism)
• HeLa Cells
• Humans
• Hydrogen-Ion Concentration
• Protective Agents (pharmacology)
• Thioredoxin-Disulfide Reductase (antagonists & inhibitors)