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Inhibition of autophagy rescues HT22 hippocampal neurons from erastin-induced ferroptosis

Neural Regeneration Research 2023年第7期18卷 1548-1552页

作者： nora hanke Abdelhaq Rami Institut für Experimentelle Neurobiologie(Anatomie Ⅱ) Klinikum der Johann Wolfgang von Goethe-UniversitätTheodor-Stern-Kai 760590 Frankfurt/MainGermany

Ferroptosis is a regulated form of cell death which is considered an oxidative iron-dependent *** lipid hydroperoxidase glutathione peroxidase 4 prevents the iron(Fe2+)-dependent formation of toxic lipid reactive oxygen *** emerging evidence indicates that inhibition of glutathione peroxidase 4 as a hallmark of ferroptosis in many cancer cell lines,the involvement of this biochemical pathway in neuronal death remains largely ***,we investigate,first whether the ferroptosis key players are involved in the neuronal cell death induced by *** second objective was to examine whether there is a cross talk between ferroptosis and *** third main was to address neuron response to erastin,with a special focus on ferritin and nuclear receptor coactivator 4-mediated *** test this in neurons,erastin(0.5-8μM)was applied to hippocampal HT22 neurons for 16 *** addition,cells were cultured with the autophagy inhibitor,3-methyladenin(10 mM)and/or ferroptosis inhibitors,ferrostatin 1(10-20μM)or deferoxamine(10-200μM)before exposure to *** this study,we demonstrated by immunofluorescence and western blot analysis,that erastin downregulates dramatically the expression of glutathione peroxidase 4,the sodium-independent cystine-glutamate antiporter and nuclear receptor coactivator *** protein levels of ferritin and mitochondrial ferritin in HT22 hippocampal neurons did not remarkably change following erastin *** addition,we demonstrated that not only the ferroptosis inhibitor,ferrostatin1/deferoxamine abrogated the ferroptotic cell death induced by erastin in hippocampal HT22 neurons,but also the potent autophagy inhibitor,*** conclude that(1)erastin-induced ferroptosis in hippocampal HT22 neurons,despite reduced nuclear receptor coactivator 4 levels,(2)that either nuclear receptor coactivator 4-mediated ferritinophagy does not occur or is of secondary importance in this model,(3)that ferroptos

关键词： erastin ferritin ferritinophagy ferroptosis glutathione peroxidase 4 HT22 neurons nuclear receptor coactivator 4

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