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Verfasst von:Campos, Joaquin [VerfasserIn]   i
 Gleitze, Silvia [VerfasserIn]   i
 Hidalgo, Cecilia [VerfasserIn]   i
 Núñez, Marco T. [VerfasserIn]   i
Titel:IP3R-mediated calcium release promotes ferroptotic death in SH-SY5Y neuroblastoma cells
Verf.angabe:Joaquín Campos, Silvia Gleitze, Cecilia Hidalgo and Marco T. Núñez
E-Jahr:2024
Jahr:4 February 2024
Umfang:18 S.
Illustrationen:Illustrationen
Fussnoten:Titel des special issue: "Oxidative stress and antioxidants in neurodegenerative disorders 2nd edition" ; Gesehen am 27.02.2025 ; Im Titel ist 3 tiefgestellt
Titel Quelle:Enthalten in: Antioxidants
Ort Quelle:Basel : MDPI, 2013
Jahr Quelle:2024
Band/Heft Quelle:13(2024), 2, special issue, Artikel-ID 196, Seite 196-1-196-18
ISSN Quelle:2076-3921
Abstract:Ferroptosis is an iron-dependent cell death pathway that involves the depletion of intracellular glutathione (GSH) levels and iron-mediated lipid peroxidation. Ferroptosis is experimentally caused by the inhibition of the cystine/glutamate antiporter xCT, which depletes cells of GSH, or by inhibition of glutathione peroxidase 4 (GPx4), a key regulator of lipid peroxidation. The events that occur between GPx4 inhibition and the execution of ferroptotic cell death are currently a matter of active research. Previous work has shown that calcium release from the endoplasmic reticulum (ER) mediated by ryanodine receptor (RyR) channels contributes to ferroptosis-induced cell death in primary hippocampal neurons. Here, we used SH-SY5Y neuroblastoma cells, which do not express RyR channels, to test if calcium release mediated by the inositol 1,4,5-trisphosphate receptor (IP3R) channel plays a role in this process. We show that treatment with RAS Selective Lethal Compound 3 (RSL3), a GPx4 inhibitor, enhanced reactive oxygen species (ROS) generation, increased cytoplasmic and mitochondrial calcium levels, increased lipid peroxidation, and caused cell death. The RSL3-induced calcium signals were inhibited by Xestospongin B, a specific inhibitor of the ER-resident IP3R calcium channel, by decreasing IP3R levels with carbachol and by IP3R1 knockdown, which also prevented the changes in cell morphology toward roundness induced by RSL3. Intracellular calcium chelation by incubation with BAPTA-AM inhibited RSL3-induced calcium signals, which were not affected by extracellular calcium depletion. We propose that GPx4 inhibition activates IP3R-mediated calcium release in SH-SY5Y cells, leading to increased cytoplasmic and mitochondrial calcium levels, which, in turn, stimulate ROS production and induce lipid peroxidation and cell death in a noxious positive feedback cycle.
DOI:doi:10.3390/antiox13020196
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.

kostenfrei: Volltext: https://doi.org/10.3390/antiox13020196
 kostenfrei: Volltext: https://www.mdpi.com/2076-3921/13/2/196
 DOI: https://doi.org/10.3390/antiox13020196
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:calcium signaling
 cell death
 endoplasmic reticulum
 ferroptosis
 glutathione peroxidase
 lipid peroxidation
 oxidative stress
 reactive oxygen species
 RSL3
K10plus-PPN:1918740763
Verknüpfungen:→ Zeitschrift

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