Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/164371
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dc.contributor.authorvon Mässenhausen, Anneen_US
dc.contributor.authorGonzalez, Nadia Zamoraen_US
dc.contributor.authorMaremonti, Francescaen_US
dc.contributor.authorBelavgeni, Alexiaen_US
dc.contributor.authorTonnus, Wulfen_US
dc.contributor.authorMeyer, Claudiaen_US
dc.contributor.authorBeer, Kristinaen_US
dc.contributor.authorHannani, Monica T.en_US
dc.contributor.authorLau, Arthuren_US
dc.contributor.authorPeitzsch, Mirkoen_US
dc.contributor.authorHoppenz, Paulen_US
dc.contributor.authorLocke, Sophieen_US
dc.contributor.authorChavakis, Triantafyllosen_US
dc.contributor.authorKramann, Rafaelen_US
dc.contributor.authorMuruve, Daniel A.en_US
dc.contributor.authorHugo, Christianen_US
dc.contributor.authorBornstein, Stefan R.en_US
dc.contributor.authorLinkermann, Andreasen_US
dc.date.accessioned2023-01-18T02:19:55Z-
dc.date.available2023-01-18T02:19:55Z-
dc.date.issued2022-
dc.identifier.citationvon Mässenhausen, A., Gonzalez, N. Z., Maremonti, F., Belavgeni, A., Tonnus, W., Meyer, C., Beer, K., Hannani, M. T., Lau, A., Peitzsch, M., Hoppenz, P., Locke, S., Chavakis, T., Kramann, R., Muruve, D. A., Hugo, C., Bornstein, S. R. & Linkermann, A. (2022). Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor-induced dipeptidase-1 expression and glutathione depletion. Science Advances, 8(5), eabl8920-. https://dx.doi.org/10.1126/sciadv.abl8920en_US
dc.identifier.issn2375-2548en_US
dc.identifier.urihttps://hdl.handle.net/10356/164371-
dc.description.abstractDexamethasone is widely used as an immunosuppressive therapy and recently as COVID-19 treatment. Here, we demonstrate that dexamethasone sensitizes to ferroptosis, a form of iron-catalyzed necrosis, previously suggested to contribute to diseases such as acute kidney injury, myocardial infarction, and stroke, all of which are triggered by glutathione (GSH) depletion. GSH levels were significantly decreased by dexamethasone. Mechanistically, we identified that dexamethasone up-regulated the GSH metabolism regulating protein dipeptidase-1 (DPEP1) in a glucocorticoid receptor (GR)-dependent manner. DPEP1 knockdown reversed the phenotype of dexamethasone-induced ferroptosis sensitization. Ferroptosis inhibitors, the DPEP1 inhibitor cilastatin, or genetic DPEP1 inactivation reversed the dexamethasone-induced increase in tubular necrosis in freshly isolated renal tubules. Our data indicate that dexamethasone sensitizes to ferroptosis by a GR-mediated increase in DPEP1 expression and GSH depletion. Together, we identified a previously unknown mechanism of glucocorticoid-mediated sensitization to ferroptosis bearing clinical and therapeutic implications.en_US
dc.language.isoenen_US
dc.relation.ispartofScience Advancesen_US
dc.rights© 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).en_US
dc.subjectScience::Medicineen_US
dc.titleDexamethasone sensitizes to ferroptosis by glucocorticoid receptor-induced dipeptidase-1 expression and glutathione depletionen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.identifier.doi10.1126/sciadv.abl8920-
dc.description.versionPublished versionen_US
dc.identifier.pmid35108055-
dc.identifier.scopus2-s2.0-85123974058-
dc.identifier.issue5en_US
dc.identifier.volume8en_US
dc.identifier.spageeabl8920en_US
dc.subject.keywordsDexamethasonesen_US
dc.subject.keywordsGlucocorticoid Receptoren_US
dc.description.acknowledgementWork in the Linkermann laboratory is funded by the SFB-TRR 205, SFB-TRR 127, and the international research training group (IRTG) 2251. This work was additionally supported by the German Research Foundation (DFG), priority program on ferroptosis (SPP2306) to A.v.M. and A.L., the Heisenberg-Professorship to A.L. (project number 324141047), and an instrument grant support to M.P. (INST 515/28-1 FUGG). We further thank the Else Kröner-Fresenius Stiftung and the Sander-Stiftung for supporting our laboratory.en_US
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