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

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• 作者：Leonie Schnell^a ; ¹ ; Lydia Dmochewitz-Kü ; ck^a ; ¹ ; Peter Feigl^a ; Cesare Montecucco^b ; ^{cesare.montecucco@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Holger Barth^a ; ^{holger.barth@uni-ulm.de" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Auranofin ; Cellular uptake ; Diphtheria toxin ; Endosome ; Membrane translocation ; Thioredoxin reductase
• 刊名：Toxicon
• 出版年：2016
• 出版时间：15 June 2016
• 年：2016
• 卷：116
• 期：Complete
• 页码：23-28
• 全文大小：802 K

文摘

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.