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Homma, T.* ; Kobayashi, S.* ; Conrad, M. ; Konno, H.* ; Yokoyama, C.* ; Fujii, J.*

Nitric oxide protects against ferroptosis by aborting the lipid peroxidation chain reaction.

Nitric oxide 115, 34-43 (2021)
Postprint DOI PMC
Open Access Green
Ferroptosis is a type of iron-dependent necrotic cell death, which is typically triggered by the depletion of intracellular glutathione (GSH), which is associated with increased lipid peroxidation. Nitric oxide (NO) is a highly reactive gaseous radical mediator with anti-oxidation properties that terminates lipid peroxidation reactions. In the current study, we report the anti-ferroptotic action of NOC18, an NO donor that spontaneously releases NO, in cells under various ferroptotic conditions in vitro. Our results indicate that, when mouse hepatoma Hepa 1–6 cells are incubated with NOC18, cell death induced by various ferroptotic stimuli such as cysteine (Cys) starvation, the inhibition of glutathione peroxidase 4 (GPX4) and treatment with tertiary-butyl hydroperoxide (TBHP) is significantly reduced. Treatment with NOC18 failed to improve the decrease in the levels of Cys or GSH and the accumulation of ferrous iron upon ferroptotic stimuli. The fluorescent intensity of C11-BODIPY581/591, a probe that is used to detect lipid peroxidation products, was increased somewhat by treatment with NOC18 under conditions of Cys starvation, and the accumulation of lipid peroxidation end-products, as evidenced by the levels of 4-hydroxynonenal, were effectively suppressed. The pre-incubation of TBHP with NOC7, a short-lived NO donor completely eliminated its ability to trigger ferroptosis. These collective results indicate that NO exerts a cytoprotective action against various ferroptotic stimuli by aborting the lipid peroxidation chain reaction.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Ferroptosis ; Glutathione ; Lipid Peroxidation ; Nitric Oxide ; Ros; Tert-butyl Hydroperoxide; Cell-death; Mediated Oxidation; Dna-damage; Peroxynitrite; Superoxide; Mechanisms; Stress; Cancer; Antioxidant
ISSN (print) / ISBN 1089-8603
e-ISSN 1089-8611
Zeitschrift Nitric oxide
Quellenangaben Band: 115, Heft: , Seiten: 34-43 Artikelnummer: , Supplement: ,
Verlag Elsevier
Verlagsort San Diego, Calif.
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Metabolism and Cell Death (MCD)
Förderungen YU-COE (C) program of Yamagata University