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

被引：15

作者：

Schnell, Leonie ^{[1
]}

Dmochewitz-Kueck, Lydia ^{[1
]}

Feigl, Peter ^{[1
]}

Montecucco, Cesare ^{[2
]}

Barth, Holger ^{[1
]}

机构：

[1] Univ Ulm, Med Ctr, Inst Pharmacol & Toxicol, Albert Einstein Allee 11, D-89081 Ulm, Germany

[2] Univ Padua, Dept Biomed Sci, Via Ugo Bassi 58-B, I-35121 Padua, Italy

来源：

TOXICON | 2016年 / 116卷

关键词：

Auranofin; Cellular uptake; Diphtheria toxin; Endosome; Membrane translocation; Thioredoxin reductase; LOW PH; BOTULINUM NEUROTOXINS; DISULFIDE BRIDGE; PLASMA-MEMBRANE; GROWTH-FACTOR; A-FRAGMENT; VERO CELLS; B-FRAGMENT; TRANSLOCATION; ENTRY;

D O I：

10.1016/j.toxicon.2015.04.012

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：23 / 28

页数：6

共 11 条

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[2] Semicarbazone EGA Inhibits Uptake of Diphtheria Toxin into Human Cells and Protects Cells from Intoxication
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[J]. ANTIOXIDANTS, 2022, 11 (07)

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