{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T23:48:56Z","timestamp":1791589736955,"version":"4.3.4"},"reference-count":55,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2022,2,4]]},"abstract":"<jats:p>\n            Dexamethasone 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)\u2013dependent manner. DPEP1 knockdown reversed the phenotype of dexamethasone-induced ferroptosis sensitization. Ferroptosis inhibitors, the DPEP1 inhibitor cilastatin, or genetic\n            <jats:italic>DPEP1<\/jats:italic>\n            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.\n          <\/jats:p>","DOI":"10.1126\/sciadv.abl8920","type":"journal-article","created":{"date-parts":[[2022,2,2]],"date-time":"2022-02-02T18:55:25Z","timestamp":1643828125000},"source":"Crossref","is-referenced-by-count":100,"title":["Dexamethasone sensitizes to ferroptosis by glucocorticoid receptor\u2013induced dipeptidase-1 expression and glutathione depletion"],"prefix":"10.1126","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-782X","authenticated-orcid":true,"given":"Anne","family":"von M\u00e4ssenhausen","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Dresden, Germany."},{"name":"Biotechnology Center, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Zamora Gonzalez","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Dresden, Germany."},{"name":"Biotechnology Center, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7670-2055","authenticated-orcid":true,"given":"Francesca","family":"Maremonti","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Dresden, Germany."},{"name":"Biotechnology Center, Technische Universit\u00e4t Dresden, 01307 Dresden, 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Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4123-6832","authenticated-orcid":true,"given":"Monica T.","family":"Hannani","sequence":"additional","affiliation":[{"name":"Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Disease, University Hospital of the RWTH Aachen, Aachen 52074, Germany."},{"name":"Heidelberg University, Faculty of Medicine, and Heidelberg University Hospital, Institute for Computational Biomedicine, Bioquant, Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3545-6756","authenticated-orcid":true,"given":"Arthur","family":"Lau","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary, Calgary, Canada."},{"name":"Snyder Institute for Chronic Disease, University of Calgary, Calgary, Canada."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirko","family":"Peitzsch","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Fetscherstrasse 74, Dresden 01307, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3437-0619","authenticated-orcid":true,"given":"Paul","family":"Hoppenz","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Dresden, Germany."},{"name":"Biotechnology Center, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Locke","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine 3, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Dresden, Germany."},{"name":"Biotechnology Center, Technische Universit\u00e4t Dresden, 01307 Dresden, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triantafyllos","family":"Chavakis","sequence":"additional","affiliation":[{"name":"Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus at the Technische Universit\u00e4t Dresden, Fetscherstrasse 74, Dresden 01307, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4048-6351","authenticated-orcid":true,"given":"Rafael","family":"Kramann","sequence":"additional","affiliation":[{"name":"Clinic for Renal and Hypertensive Disorders, Rheumatological and Immunological Disease, University Hospital of the RWTH Aachen, Aachen 52074, Germany."},{"name":"Department of Internal Medicine, Nephrology and Transplantation, Erasmus Medical Center, 3015 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