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

2016
Authors
Wedmann, RudolfOnderka, Constantin
Wei, Shengwei
Szijarto, Istvan Andras
Miljković, Jan Lj
Mitrović, Aleksandra D.

Lange, Mike
Savitsky, Sergey
Yadav, Pramod Kumar

Torregrossa, Roberta
Harrer, Ellen G.
Harrer, Thomas
Ishii, Isao

Gollasch, Maik
Wood, Mark E.

Galardon, Erwan

Xian, Ming
Whiteman, Matthew

Banerjee, Ruma
Filipović, Miloš R.

Article (Published version)
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Show full item recordAbstract
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 cau...sed 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.
Source:
Chemical Science, 2016, 7, 5, 3414-3426Publisher:
- Royal Soc Chemistry, Cambridge
Funding / projects:
- Medical Research Council [MR/M022706/1]
- French State in the frame of the Investments for the future Programme IdEx Bordeaux [ANR-10-IDEX-03-02]
- Deutsche Forschungsgemeinschaft
- Dr Werner Jackstadt-Stiftung
- American Heart Association [14POST18760003]
- Friedrich-Alexander University within the Emerging Field Initiative (MRIC)
- Brian Ridge Scholarship
- National Institutes of Health [HL58984, GM112455, NIH R01HL116571]
Note:
- Supplementary material: http://cherry.chem.bg.ac.rs/handle/123456789/3543
DOI: 10.1039/c5sc04818d
ISSN: 2041-6520
PubMed: 27170841
WoS: 000374859300056
Scopus: 2-s2.0-84966356269
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Wedmann, Rudolf AU - Onderka, Constantin AU - Wei, Shengwei AU - Szijarto, Istvan Andras AU - Miljković, Jan Lj AU - Mitrović, Aleksandra D. AU - Lange, Mike AU - Savitsky, Sergey AU - Yadav, Pramod Kumar AU - Torregrossa, Roberta AU - Harrer, Ellen G. AU - Harrer, Thomas AU - Ishii, Isao AU - Gollasch, Maik AU - Wood, Mark E. AU - Galardon, Erwan AU - Xian, Ming AU - Whiteman, Matthew AU - Banerjee, Ruma AU - Filipović, Miloš R. PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/1925 AB - 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. PB - Royal Soc Chemistry, Cambridge T2 - Chemical Science T1 - Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation VL - 7 IS - 5 SP - 3414 EP - 3426 DO - 10.1039/c5sc04818d ER -
@article{ author = "Wedmann, Rudolf and Onderka, Constantin and Wei, Shengwei and Szijarto, Istvan Andras and Miljković, Jan Lj and Mitrović, Aleksandra D. and Lange, Mike and Savitsky, Sergey and Yadav, Pramod Kumar and Torregrossa, Roberta and Harrer, Ellen G. and Harrer, Thomas and Ishii, Isao and Gollasch, Maik and Wood, Mark E. and Galardon, Erwan and Xian, Ming and Whiteman, Matthew and Banerjee, Ruma and Filipović, Miloš R.", year = "2016", 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.", publisher = "Royal Soc Chemistry, Cambridge", journal = "Chemical Science", title = "Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation", volume = "7", number = "5", pages = "3414-3426", doi = "10.1039/c5sc04818d" }
Wedmann, R., Onderka, C., Wei, S., Szijarto, I. A., Miljković, J. L., Mitrović, A. D., Lange, M., Savitsky, S., Yadav, P. K., Torregrossa, R., Harrer, E. G., Harrer, T., Ishii, I., Gollasch, M., Wood, M. E., Galardon, E., Xian, M., Whiteman, M., Banerjee, R.,& Filipović, M. R.. (2016). Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation. in Chemical Science Royal Soc Chemistry, Cambridge., 7(5), 3414-3426. https://doi.org/10.1039/c5sc04818d
Wedmann R, Onderka C, Wei S, Szijarto IA, Miljković JL, Mitrović AD, 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, Filipović MR. Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation. in Chemical Science. 2016;7(5):3414-3426. doi:10.1039/c5sc04818d .
Wedmann, Rudolf, Onderka, Constantin, Wei, Shengwei, Szijarto, Istvan Andras, Miljković, Jan Lj, Mitrović, Aleksandra D., Lange, Mike, Savitsky, Sergey, Yadav, Pramod Kumar, Torregrossa, Roberta, Harrer, Ellen G., Harrer, Thomas, Ishii, Isao, Gollasch, Maik, Wood, Mark E., Galardon, Erwan, Xian, Ming, Whiteman, Matthew, Banerjee, Ruma, Filipović, Miloš R., "Improved tag-switch method reveals that thioredoxin acts as depersulfidase and controls the intracellular levels of protein persulfidation" in Chemical Science, 7, no. 5 (2016):3414-3426, https://doi.org/10.1039/c5sc04818d . .