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Canli, Ö.* ; Alankus, Y.B.* ; Grootjans, S.* ; Vegi, N.* ; Hültner, L. ; Hoppe, P.S. ; Schroeder, T.* ; Vandenabeele, P.* ; Bornkamm, G.W. ; Greten, F.R.*

Glutathione peroxidase 4 prevents necroptosis in mouse erythroid precursors.

Blood 127, 139-148 (2016)
Verlagsversion Postprint DOI PMC
Open Access Green
Maintaining cellular redox balance is vital for cell survival and tissue homoeostasis since imbalanced production of ROS may lead to oxidative stress and cell death. The anti-oxidant enzyme glutathione peroxidase 4 (Gpx4) is a key regulator of oxidative stress-induced cell death. We show that mice with deletion of Gpx4 in hematopoietic cells develop anemia and that it is essential for preventing RIP3 dependent necroptosis in erythroid precursor cells. Absence of Gpx4 leads to functional inactivation of caspase 8 by glutathionylation. This results in necroptosis, which occurs independently of TNFα activation. While genetic ablation of Rip3 normalizes reticulocyte maturation and prevents anemia, ROS accumulation and lipid peroxidation in Gpx4 deficient cells remain high. Our results demonstrate that ROS and lipid hydroperoxides function as so far unrecognized unconventional upstream signaling activators of RIP3-dependent necroptosis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Gpx4 Is Essential For Preventing Anemia In Mice Via Inhibiting Rip3-dependent Necroptosis In Erythroid Precursor Cells ; Ros Accumulation And Lipid Peroxidation In Erythroid Precursor Cells Trigger Receptor-independent Activation Of Necroptosis; Tumor-necrosis-factor; Cell-death; Programmed Necrosis; Hydrogen-peroxide; Inflammation; Apoptosis; Mice; Homeostasis; Ferroptosis; Protects
Sprache englisch
Veröffentlichungsjahr 2016
Prepublished im Jahr 2015
HGF-Berichtsjahr 2015
ISSN (print) / ISBN 0006-4971
e-ISSN 1528-0020
Zeitschrift Blood
Quellenangaben Band: 127, Heft: 1, Seiten: 139-148 Artikelnummer: , Supplement: ,
Verlag American Society of Hematology
Verlagsort Washington
Begutachtungsstatus Peer reviewed
POF Topic(s) 30204 - Cell Programming and Repair
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Stem Cell and Neuroscience
Immune Response and Infection
PSP-Element(e) G-500800-001
G-501400-006
G-501490-001
G-501400-005
Scopus ID 84955476379
PubMed ID 26463424
Erfassungsdatum 2015-11-04