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Verfasst von:Gleitze, Silvia [VerfasserIn]   i
 Ramirez, Omar [VerfasserIn]   i
 Vega-Vásquez, Ignacio [VerfasserIn]   i
 Yan, Jing [VerfasserIn]   i
 Lobos, Pedro [VerfasserIn]   i
 Bading, Hilmar [VerfasserIn]   i
 Núñez, Marco T. [VerfasserIn]   i
 Paula-Lima, Andrea [VerfasserIn]   i
 Hidalgo, Cecilia [VerfasserIn]   i
Titel:Ryanodine receptor mediated calcium release contributes to ferroptosis induced in primary hippocampal neurons by GPX4 inhibition
Verf.angabe:Silvia Gleitze, Omar A. Ramírez, Ignacio Vega-Vásquez, Jing Yan, Pedro Lobos, Hilmar Bading, Marco T. Núñez, Andrea Paula-Lima and Cecilia Hidalgo
E-Jahr:2023
Jahr:13 March 2023
Umfang:18 S.
Fussnoten:Gesehen am 24.11.2023
Titel Quelle:Enthalten in: Antioxidants
Ort Quelle:Basel : MDPI, 2013
Jahr Quelle:2023
Band/Heft Quelle:12(2023), 3, Artikel-ID 705, Seite 1-18
ISSN Quelle:2076-3921
Abstract:Ferroptosis, a newly described form of regulated cell death, is characterized by the iron-dependent accumulation of lipid peroxides, glutathione depletion, mitochondrial alterations, and enhanced lipoxygenase activity. Inhibition of glutathione peroxidase 4 (GPX4), a key intracellular antioxidant regulator, promotes ferroptosis in different cell types. Scant information is available on GPX4-induced ferroptosis in hippocampal neurons. Moreover, the role of calcium (Ca2+) signaling in ferroptosis remains elusive. Here, we report that RSL3, a selective inhibitor of GPX4, caused dendritic damage, lipid peroxidation, and induced cell death in rat primary hippocampal neurons. Previous incubation with the ferroptosis inhibitors deferoxamine or ferrostatin-1 reduced these effects. Likewise, preincubation with micromolar concentrations of ryanodine, which prevent Ca2+ release mediated by Ryanodine Receptor (RyR) channels, partially protected against RSL3-induced cell death. Incubation with RSL3 for 24 h suppressed the cytoplasmic Ca2+ concentration increase induced by the RyR agonist caffeine or by the SERCA inhibitor thapsigargin and reduced hippocampal RyR2 protein content. The present results add to the current understanding of ferroptosis-induced neuronal cell death in the hippocampus and provide new information both on the role of RyR-mediated Ca2+ signals on this process and on the effects of GPX4 inhibition on endoplasmic reticulum calcium content.
DOI:doi:10.3390/antiox12030705
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.3390/antiox12030705
 Volltext: https://www.mdpi.com/2076-3921/12/3/705
 DOI: https://doi.org/10.3390/antiox12030705
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:calcium signaling
 cell death
 dendritic morphology
 endoplasmic reticulum
 ferroptosis
 glutathione peroxidase
 iron
 iron chelators
 lipid peroxidation
 neurodegeneration
 oxidative stress
 reactive oxygen species
 RSL3
K10plus-PPN:187104443X
Verknüpfungen:→ Zeitschrift

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