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License: CC BY NC
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https://doi.org/10.1039/c5sc04...
Article . 2016 . Peer-reviewed
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Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation

Authors: Rudolf Wedmann; Constantin Onderka; Shengwei Wei; István András Szijártó; Jan Lj. Miljkovic; Aleksandra Mitrovic; Mike Lange; +13 Authors

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

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.

Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3543]

Countries
Serbia, Germany
Subjects by Vocabulary

Microsoft Academic Graph classification: Regulator Cystine Inflammation Oxidative phosphorylation Biology law.invention chemistry.chemical_compound law medicine Cell biology Biochemistry chemistry Recombinant DNA Thioredoxin medicine.symptom Intracellular Cysteine

Dewey Decimal Classification: ddc:540

Keywords

-, General Chemistry, Naturwissenschaftliche Fakultät, Cardiovascular and Metabolic Diseases

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
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influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
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