Journal article
Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation
Chemical science (Cambridge), Vol.7(5), pp.3414-3426
05/25/2016
Handle:
https://hdl.handle.net/2376/106662
PMID: 27170841
Abstract
Hydrogen sulfide (H
S) 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
-sulfhydration) has been proposed as the main pathway for H
S-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 H
S release suggesting that thioredoxin could be an important regulator of H
S levels from persulfide pools. Inhibition of the thioredoxin system caused an increase in intracellular persulfides, highlighting thioredoxin as a major protein depersulfidase that controls H
S signalling. Finally, using plasma from HIV-1 patients that have higher circulatory levels of thioredoxin, we could prove depersulfidase role
.
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Details
- Title
- Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation
- Creators
- Rudolf Wedmann - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.frConstantin Onderka - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.frShengwei Wei - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.frIstván András Szijártó - Charité Campus Virchow , Nephrology/Intensive Care , Berlin , GermanyJan Lj Miljkovic - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.frAleksandra Mitrovic - Department of Chemistry , University of Belgrade , Belgrade , SerbiaMike Lange - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.frSergey Savitsky - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.frPramod Kumar Yadav - Department of Biological Chemistry , University of Michigan , Ann Arbor , USARoberta Torregrossa - University of Exeter Medical School , St. Luke's Campus , Exeter , UK ; Biosciences , College of Life and Environmental Sciences of Biosciences , University of Exeter , Streatham Campus , Exeter , Devon , UKEllen G Harrer - Infectious Diseases Section , Department of Internal Medicine 3 , Universitätsklinikum Erlangen , Friedrich-Alexander-University, Erlangen-Nürnberg , GermanyThomas Harrer - Infectious Diseases Section , Department of Internal Medicine 3 , Universitätsklinikum Erlangen , Friedrich-Alexander-University, Erlangen-Nürnberg , GermanyIsao Ishii - Department of Biochemistry , Graduate School of Pharmaceutical Sciences , Keio University , Tokyo , JapanMaik Gollasch - Charité Campus Virchow , Nephrology/Intensive Care , Berlin , GermanyMark E Wood - Biosciences , College of Life and Environmental Sciences of Biosciences , University of Exeter , Streatham Campus , Exeter , Devon , UKErwan Galardon - UMR CNRS 8601 , Université Paris Descartes , Sorbonne Paris Cité , Paris , FranceMing Xian - Department of Chemistry , Washington State University , Pullman , USAMatthew Whiteman - University of Exeter Medical School , St. Luke's Campus , Exeter , UKRuma Banerjee - Department of Biological Chemistry , University of Michigan , Ann Arbor , USAMilos R Filipovic - Department of Chemistry and Pharmacy , Friedrich-Alexander University of Erlangen-Nuremberg , Erlangen , Germany . Email: milos.filipovic@ibgc.cnrs.fr; Université de Bordeaux , IBGC , UMR 5095 , F-33077 Bordeaux , France ; CNRS , IBGC , UMR 5095 , F-33077 Bordeaux , France
- Publication Details
- Chemical science (Cambridge), Vol.7(5), pp.3414-3426
- Academic Unit
- Chemistry, Department of; Biological Chemistry, Institute of
- Publisher
- England
- Grant note
- R01 HL058984 / NHLBI NIH HHS R01 HL116571 / NHLBI NIH HHS R01 GM112455 / NIGMS NIH HHS
- Identifiers
- 99900547161101842
- Language
- English
- Resource Type
- Journal article