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

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): 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
Zeitschrift: Chemical Science
Jahr der Veröffentlichung: 2016
Band: 7
Heftnummer: 5
Seitenbereich: 3414-3426
ISSN: 2041-6520


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.



FAU-Autoren / FAU-Herausgeber

Filipovic, Milos
Lehrstuhl für Bioanorganische Chemie
Harrer, Thomas Prof. Dr.
Professur für Innere Medizin mit dem Schwerpunkt Immundefizienz
Miljkovic, Jan
Lehrstuhl für Bioanorganische Chemie
Onderka, Constantin
Lehrstuhl für Bioanorganische Chemie
Wedmann, Rudolf
Lehrstuhl für Bioanorganische Chemie
Wei, Shengwei Dr.
Lehrstuhl für Bioanorganische Chemie


Autor(en) der externen Einrichtung(en)
Charité - Universitätsmedizin Berlin
Keio University / 慶應義塾大学
Universität Paris Descartes / Université Paris 5 René Descartes
University of Belgrade / Универзитет у Београду
University of Exeter
University of Michigan
Washington State University (WSU)


Zitierweisen

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://dx.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.

BibTeX: 

Zuletzt aktualisiert 2018-10-10 um 02:18