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doi:10.22028/D291-39047
Titel: | Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism |
VerfasserIn: | Chen, F. Elgaher, W. A.M. Winterhoff, M. Büssow, K. Waqas, F. H. Graner, E. Pires-Afonso, Y. Casares Perez, L. de la Vega, L. Sahini, N. Czichon, L. Zobl, W. Zillinger, T. Shehata, M. Pleschka, S. Bähre, H. Falk, C. Michelucci, A. Schuchardt, S. Blankenfeldt, W. Hirsch, A. K. H. Pessler, F. |
Sprache: | Englisch |
Titel: | Nature Metabolism |
Bandnummer: | 4 |
Heft: | 5 |
Seiten: | 534-546 |
Verlag/Plattform: | Springer Nature |
Erscheinungsjahr: | 2022 |
Freie Schlagwörter: | Applied immunology Immunology Metabolism Metabolomics |
DDC-Sachgruppe: | 500 Naturwissenschaften |
Dokumenttyp: | Journalartikel / Zeitschriftenartikel |
Abstract: | Although the immunomodulatory and cytoprotective properties of itaconate have been studied extensively, it is not known whether its naturally occurring isomers mesaconate and citraconate have similar properties. Here, we show that itaconate is partially converted to mesaconate intracellularly and that mesaconate accumulation in macrophage activation depends on prior itaconate synthesis. When added to human cells in supraphysiological concentrations, all three isomers reduce lactate levels, whereas itaconate is the strongest succinate dehydrogenase (SDH) inhibitor. In cells infected with influenza A virus (IAV), all three isomers profoundly alter amino acid metabolism, modulate cytokine/chemokine release and reduce interferon signalling, oxidative stress and the release of viral particles. Of the three isomers, citraconate is the strongest electrophile and nuclear factor-erythroid 2-related factor 2 (NRF2) agonist. Only citraconate inhibits catalysis of itaconate by cis-aconitate decarboxylase (ACOD1), probably by competitive binding to the substrate-binding site. These results reveal mesaconate and citraconate as immunomodulatory, anti-oxidative and antiviral compounds, and citraconate as the first naturally occurring ACOD1 inhibitor. |
DOI der Erstveröffentlichung: | 10.1038/s42255-022-00577-x |
URL der Erstveröffentlichung: | https://www.nature.com/articles/s42255-022-00577-x |
Link zu diesem Datensatz: | urn:nbn:de:bsz:291--ds-390478 hdl:20.500.11880/35215 http://dx.doi.org/10.22028/D291-39047 |
ISSN: | 2522-5812 |
Datum des Eintrags: | 15-Feb-2023 |
Bezeichnung des in Beziehung stehenden Objekts: | Supplementary information |
In Beziehung stehendes Objekt: | https://static-content.springer.com/esm/art%3A10.1038%2Fs42255-022-00577-x/MediaObjects/42255_2022_577_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs42255-022-00577-x/MediaObjects/42255_2022_577_MOESM2_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs42255-022-00577-x/MediaObjects/42255_2022_577_MOESM3_ESM.xlsx https://static-content.springer.com/esm/art%3A10.1038%2Fs42255-022-00577-x/MediaObjects/42255_2022_577_MOESM4_ESM.xlsx https://static-content.springer.com/esm/art%3A10.1038%2Fs42255-022-00577-x/MediaObjects/42255_2022_577_MOESM5_ESM.pdf |
Fakultät: | NT - Naturwissenschaftlich- Technische Fakultät |
Fachrichtung: | NT - Pharmazie |
Professur: | NT - Prof. Dr. Anna Hirsch |
Sammlung: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Dateien zu diesem Datensatz:
Datei | Beschreibung | Größe | Format | |
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s42255-022-00577-x.pdf | 13,99 MB | Adobe PDF | Öffnen/Anzeigen |
Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons