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Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation

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Item Type:Article
Title:Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation
Creators Name:Wedmann, R. and Onderka, C. and Wei, S. and Szijártó, I.A. and Miljkovic, J.L. and Mitrovic, A. and Lange, M. and Savitsky, S. and Yadav, P.K. and Torregrossa, R. and Harrer, E.G. and Harrer, T. and Ishii, I. and Gollasch, M. and Wood, M.E. and Galardon, E. and Xian, M. and Whiteman, M. and Banerjee, R. and Filipovic, M.R.
Abstract:Hydrogen sulfide (H2S) has emerged as a signalling molecule capable of regulating several important physiological functions such as blood pressure, neurotransmission and inflammation. The mechanisms behind these effects are still largely elusive and oxidative posttranslational modification of cysteine residues (protein persulfidation or S-sulfhydration) has been proposed as the main pathway for H2S-induced biological and pharmacological effects. As a signalling mechanism, persulfidation has to be controlled. Using an improved tag-switch assay for persulfide detection we show here that protein persulfide levels are controlled by the thioredoxin system. Recombinant thioredoxin showed an almost 10-fold higher reactivity towards cysteine persulfide than towards cystine and readily cleaved protein persulfides as well. This reaction resulted in H2S release suggesting that thioredoxin could be an important regulator of H2S levels from persulfide pools. Inhibition of the thioredoxin system caused an increase in intracellular persulfides, highlighting thioredoxin as a major protein depersulfidase that controls H2S signalling. Finally, using plasma from HIV-1 patients that have higher circulatory levels of thioredoxin, we could prove depersulfidase role in vivo.
Keywords:Animals, Mice
Source:Chemical Science
ISSN:2041-6520
Publisher:Royal Society of Chemistry (U.K.)
Volume:7
Number:5
Page Range:3414-3426
Date:25 May 2016
Official Publication:https://doi.org/10.1039/c5sc04818d
PubMed:View item in PubMed

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