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7-Dehydrocholesterol is an endogenous suppressor of ferroptosis.

التفاصيل البيبلوغرافية
العنوان: 7-Dehydrocholesterol is an endogenous suppressor of ferroptosis.
المؤلفون: Freitas FP; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Alborzinia H; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Dos Santos AF; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Nepachalovich P; Center of Membrane Biochemistry and Lipid Research, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany., Pedrera L; Institute of Genetics, CECAD, University of Cologne, Cologne, Germany., Zilka O; Department of Chemistry & Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada., Inague A; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany.; Instituto de Química, Universidade de Sao Paulo, Sao Paulo, Brazil., Klein C; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Aroua N; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Kaushal K; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Kast B; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany., Lorenz SM; Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany., Kunz V; Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany., Nehring H; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Xavier da Silva TN; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Chen Z; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Atici S; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany., Doll SG; Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany., Schaefer EL; Department of Chemistry & Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada., Ekpo I; Department of Chemistry & Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada., Schmitz W; Department of Biochemistry and Molecular Biology, Theodor Boveri Institute, Biocenter, University of Würzburg, Würzburg, Germany., Horling A; Institute of Pharmacy, Martin Luther University Halle Wittenberg, Halle, Germany., Imming P; Institute of Pharmacy, Martin Luther University Halle Wittenberg, Halle, Germany., Miyamoto S; Instituto de Química, Universidade de Sao Paulo, Sao Paulo, Brazil., Wehman AM; Department of Biological Sciences, University of Denver, Denver, CO, USA., Genaro-Mattos TC; Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA., Mirnics K; Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE, USA., Kumar L; Faculty of Applied Sciences and Biotechnology, Shoolini University, Himachal Pradesh, India., Klein-Seetharaman J; Department of Physics, Colorado School of Mines, Golden, CO, USA.; School of Molecular Sciences, Arizona State University, Phoenix, AZ, USA., Meierjohann S; Department of Pathology, University of Würzburg, Würzburg, Germany., Weigand I; Medizinische Klinik und Poliklinik IV, Ludwig Maximillian University, Munich, Germany., Kroiss M; Medizinische Klinik und Poliklinik IV, Ludwig Maximillian University, Munich, Germany., Bornkamm GW; Institute of Experimental Cancer Research, University Hospital Ulm, Ulm, Germany., Gomes F; Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil., Netto LES; Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil., Sathian MB; Department of Pharmacy, Ludwig Maximilian University of Munich, Munich, Germany., Konrad DB; Department of Pharmacy, Ludwig Maximilian University of Munich, Munich, Germany., Covey DF; Department of Developmental Biology, Washington University in St. Louis, St. Louis, MO, USA.; Taylor Family Institute for Innovative Psychiatric Research, Washington University, St. Louis, MO, USA., Michalke B; Research Unit Analytical BioGeoChemistry, Helmholtz Center München (HMGU), Neuherberg, Germany., Bommert K; Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany., Bargou RC; Comprehensive Cancer Center Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany., Garcia-Saez A; Institute of Genetics, CECAD, University of Cologne, Cologne, Germany., Pratt DA; Department of Chemistry & Biomolecular Sciences, University of Ottawa, Ottawa, Ontario, Canada., Fedorova M; Center of Membrane Biochemistry and Lipid Research, University Hospital and Faculty of Medicine Carl Gustav Carus of TU Dresden, Dresden, Germany., Trumpp A; Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM gGmbH), Heidelberg, Germany.; Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ) and DKFZ-ZMBH Alliance, Heidelberg, Germany.; German Cancer Consortium (DKTK), Heidelberg, Germany., Conrad M; Institute of Metabolism and Cell Death, Helmholtz Zentrum München, Neuherberg, Germany., Friedmann Angeli JP; Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Germany. pedro.angeli@uni-wuerzburg.de.
المصدر: Nature [Nature] 2024 Feb; Vol. 626 (7998), pp. 401-410. Date of Electronic Publication: 2024 Jan 31.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE
أسماء مطبوعة: Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.
مواضيع طبية MeSH: Burkitt Lymphoma*/metabolism , Burkitt Lymphoma*/pathology , Dehydrocholesterols*/metabolism , Ferroptosis* , Neuroblastoma*/metabolism , Neuroblastoma*/pathology, Animals ; Humans ; Cell Survival ; Lipid Peroxidation ; Neoplasm Transplantation ; Oxidation-Reduction ; Phenotype ; Reproducibility of Results
مستخلص: Ferroptosis is a form of cell death that has received considerable attention not only as a means to eradicate defined tumour entities but also because it provides unforeseen insights into the metabolic adaptation that tumours exploit to counteract phospholipid oxidation 1,2 . Here, we identify proferroptotic activity of 7-dehydrocholesterol reductase (DHCR7) and an unexpected prosurvival function of its substrate, 7-dehydrocholesterol (7-DHC). Although previous studies suggested that high concentrations of 7-DHC are cytotoxic to developing neurons by favouring lipid peroxidation 3 , we now show that 7-DHC accumulation confers a robust prosurvival function in cancer cells. Because of its far superior reactivity towards peroxyl radicals, 7-DHC effectively shields (phospho)lipids from autoxidation and subsequent fragmentation. We provide validation in neuroblastoma and Burkitt's lymphoma xenografts where we demonstrate that the accumulation of 7-DHC is capable of inducing a shift towards a ferroptosis-resistant state in these tumours ultimately resulting in a more aggressive phenotype. Conclusively, our findings provide compelling evidence of a yet-unrecognized antiferroptotic activity of 7-DHC as a cell-intrinsic mechanism that could be exploited by cancer cells to escape ferroptosis.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
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المشرفين على المادة: BK1IU07GKF (7-dehydrocholesterol)
EC 1.3.1.21 (7-dehydrocholesterol reductase)
0 (Dehydrocholesterols)
3170-83-0 (perhydroxyl radical)
تواريخ الأحداث: Date Created: 20240131 Date Completed: 20240213 Latest Revision: 20240213
رمز التحديث: 20240213
DOI: 10.1038/s41586-023-06878-9
PMID: 38297129
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-4687
DOI:10.1038/s41586-023-06878-9