Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols
Nitrosation of critical thiols has been elaborated as reversible posttranslational modification with regulatory function in multiple disorders. Reversibility of S-nitrosation is generally associated with enzyme-mediated one-electron reductions, catalyzed by the thioredoxin system, or by nitrosogluta...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-10-01
|
| Series: | Redox Biology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722002117 |
| _version_ | 1797995424946061312 |
|---|---|
| author | Stefan Schildknecht Alex von Kriegsheim Ksenija Vujacic-Mirski Fabio Di Lisa Volker Ullrich Andreas Daiber |
| author_facet | Stefan Schildknecht Alex von Kriegsheim Ksenija Vujacic-Mirski Fabio Di Lisa Volker Ullrich Andreas Daiber |
| author_sort | Stefan Schildknecht |
| collection | DOAJ |
| description | Nitrosation of critical thiols has been elaborated as reversible posttranslational modification with regulatory function in multiple disorders. Reversibility of S-nitrosation is generally associated with enzyme-mediated one-electron reductions, catalyzed by the thioredoxin system, or by nitrosoglutathione reductase.In the present study, we confirm previous evidence for a non-enzymatic de-nitrosation of nitrosoglutathione (GSNO) by superoxide. The interaction leads to the release of nitric oxide that subsequently interacts with a second molecule of superoxide (O2•−) to form peroxynitrite. Despite the formation of peroxynitrite, approximately 40–70% of GSNO yielded reduced glutathione (GSH), depending on the applied analytical assay. The concept of O2•− dependent denitrosation was then applied to S-nitrosated enzymes. S-nitrosation of isocitrate dehydrogenase (ICDH; NADP+-dependent) was accompanied by an inhibition of the enzyme and could be reversed by dithiothreitol. Treatment of nitrosated ICDH with O2•− indicated ca. 50% recovery of enzyme activity. Remaining inhibition was largely consequence of oxidative modifications evoked either by O2•− or by peroxynitrite. Recovery of activity in S-nitrosated enzymes by O2•− appears relevant only for selected examples. In contrast, recovery of reduced glutathione from the interaction of GSNO with O2•− could represent a mechanism to regain reducing equivalents in situations of excess O2•− formation, e.g. in the reperfusion phase after ischemia. |
| first_indexed | 2024-04-11T10:01:25Z |
| format | Article |
| id | doaj.art-1971799c2c774bbe932b5cd4885368b4 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-11T10:01:25Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-1971799c2c774bbe932b5cd4885368b42022-12-22T04:30:25ZengElsevierRedox Biology2213-23172022-10-0156102439Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiolsStefan Schildknecht0Alex von Kriegsheim1Ksenija Vujacic-Mirski2Fabio Di Lisa3Volker Ullrich4Andreas Daiber5Albstadt-Sigmaringen University, Faculty of Life Sciences, 72488, Sigmaringen, Germany; Corresponding author. Department of Life Sciences, Albstadt-Sigmaringen University of Applied Sciences, 72488, Sigmaringen, Germany.Institute of Genetics and Cancer, University of Edinburgh, UKCenter for Cardiology, Department of Cardiology 1, Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg University, 55131, Mainz, GermanyDepartment of Biomedical Sciences, University of Padova, Padova, ItalyAlbstadt-Sigmaringen University, Faculty of Life Sciences, 72488, Sigmaringen, Germany; Institute of Genetics and Cancer, University of Edinburgh, UK; Center for Cardiology, Department of Cardiology 1, Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg University, 55131, Mainz, Germany; Department of Biomedical Sciences, University of Padova, Padova, Italy; Partner Site Rhine-Main, German Center for Cardiovascular Research (DZHK), Langenbeckstr. 1, 55131, Mainz, Germany; Department of Biology, University of Konstanz, GermanyCenter for Cardiology, Department of Cardiology 1, Laboratory of Molecular Cardiology, University Medical Center of the Johannes Gutenberg University, 55131, Mainz, Germany; Partner Site Rhine-Main, German Center for Cardiovascular Research (DZHK), Langenbeckstr. 1, 55131, Mainz, Germany; Corresponding author. Universitätsmedizin der Johannes Gutenberg-Universität Zentrum für Kardiologie 1 – Labor für Molekulare Kardiologie, Geb. 605 – Raum 3.262, Langenbeckstr. 1, 55131, Mainz, Germany.Nitrosation of critical thiols has been elaborated as reversible posttranslational modification with regulatory function in multiple disorders. Reversibility of S-nitrosation is generally associated with enzyme-mediated one-electron reductions, catalyzed by the thioredoxin system, or by nitrosoglutathione reductase.In the present study, we confirm previous evidence for a non-enzymatic de-nitrosation of nitrosoglutathione (GSNO) by superoxide. The interaction leads to the release of nitric oxide that subsequently interacts with a second molecule of superoxide (O2•−) to form peroxynitrite. Despite the formation of peroxynitrite, approximately 40–70% of GSNO yielded reduced glutathione (GSH), depending on the applied analytical assay. The concept of O2•− dependent denitrosation was then applied to S-nitrosated enzymes. S-nitrosation of isocitrate dehydrogenase (ICDH; NADP+-dependent) was accompanied by an inhibition of the enzyme and could be reversed by dithiothreitol. Treatment of nitrosated ICDH with O2•− indicated ca. 50% recovery of enzyme activity. Remaining inhibition was largely consequence of oxidative modifications evoked either by O2•− or by peroxynitrite. Recovery of activity in S-nitrosated enzymes by O2•− appears relevant only for selected examples. In contrast, recovery of reduced glutathione from the interaction of GSNO with O2•− could represent a mechanism to regain reducing equivalents in situations of excess O2•− formation, e.g. in the reperfusion phase after ischemia.http://www.sciencedirect.com/science/article/pii/S2213231722002117S-nitros(yl)ationS-denitrosationSuperoxideNitric oxideIschemia/reperfusion |
| spellingShingle | Stefan Schildknecht Alex von Kriegsheim Ksenija Vujacic-Mirski Fabio Di Lisa Volker Ullrich Andreas Daiber Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols Redox Biology S-nitros(yl)ation S-denitrosation Superoxide Nitric oxide Ischemia/reperfusion |
| title | Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols |
| title_full | Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols |
| title_fullStr | Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols |
| title_full_unstemmed | Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols |
| title_short | Recovery of reduced thiol groups by superoxide-mediated denitrosation of nitrosothiols |
| title_sort | recovery of reduced thiol groups by superoxide mediated denitrosation of nitrosothiols |
| topic | S-nitros(yl)ation S-denitrosation Superoxide Nitric oxide Ischemia/reperfusion |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722002117 |
| work_keys_str_mv | AT stefanschildknecht recoveryofreducedthiolgroupsbysuperoxidemediateddenitrosationofnitrosothiols AT alexvonkriegsheim recoveryofreducedthiolgroupsbysuperoxidemediateddenitrosationofnitrosothiols AT ksenijavujacicmirski recoveryofreducedthiolgroupsbysuperoxidemediateddenitrosationofnitrosothiols AT fabiodilisa recoveryofreducedthiolgroupsbysuperoxidemediateddenitrosationofnitrosothiols AT volkerullrich recoveryofreducedthiolgroupsbysuperoxidemediateddenitrosationofnitrosothiols AT andreasdaiber recoveryofreducedthiolgroupsbysuperoxidemediateddenitrosationofnitrosothiols |