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

Wedmann R, Onderka C, Wei S, Szijarto IA, Miljkovic J, Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, Harrer EG, Harrer T, Ishii I, Gollasch M, Wood ME, Galardon E, Xian M, Whiteman M, Banerjee R, Filipovic M (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Book Volume: 7

Pages Range: 3414-3426

Journal Issue: 5

DOI: 10.1039/c5sc04818d

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.

Authors with CRIS profile

Involved external institutions

Charité - Universitätsmedizin Berlin Germany (DE) University of Exeter United Kingdom (GB) University of Paris 5 - René Descartes / Université Paris V René Descartes France (FR) Washington State University (WSU) United States (USA) (US) University of Michigan United States (USA) (US) University of Belgrade / Универзитет у Београду Serbia (RS) Keio University / 慶應義塾大学 Japan (JP)

How to cite

APA:

Wedmann, R., Onderka, C., Wei, S., Szijarto, I.A., Miljkovic, J., Mitrovic, A.,... Filipovic, M. (2016). Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation. Chemical Science, 7(5), 3414-3426. https://doi.org/10.1039/c5sc04818d

MLA:

Wedmann, Rudolf, et al. "Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation." Chemical Science 7.5 (2016): 3414-3426.

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