Neuronal autosis is Na+/K+-ATPase alpha 3-dependent and involved in hypoxic-ischemic neuronal death.

Détails

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Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_7E072BA1C461
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Neuronal autosis is Na+/K+-ATPase alpha 3-dependent and involved in hypoxic-ischemic neuronal death.
Périodique
Cell death & disease
Auteur⸱e⸱s
Depierre P., Ginet V., Truttmann A.C., Puyal J.
ISSN
2041-4889 (Electronic)
Statut éditorial
Publié
Date de publication
25/05/2024
Peer-reviewed
Oui
Volume
15
Numéro
5
Pages
363
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Macroautophagy (hereafter called autophagy) is an essential physiological process of degradation of organelles and long-lived proteins. The discovery of autosis, a Na <sup>+</sup> /K <sup>+</sup> -ATPase (ATP1)-dependent type of autophagic cell death with specific morphological and biochemical features, has strongly contributed to the acceptance of a pro-death role of autophagy. However, the occurrence and relevance of autosis in neurons has never been clearly investigated, whereas we previously provided evidence that autophagy mechanisms could be involved in neuronal death in different in vitro and in vivo rodent models of hypoxia-ischemia (HI) and that morphological features of autosis were observed in dying neurons following rat perinatal cerebral HI. In the present study, we demonstrated that neuronal autosis could occur in primary cortical neurons using two different stimulations enhancing autophagy flux and neuronal death: a neurotoxic concentration of Tat-BECN1 (an autophagy-inducing peptide) and a hypoxic/excitotoxic stimulus (mimicking neuronal death induced by cerebral HI). Both stimulations induce autophagic neuronal death (dependent on canonical autophagic genes and independent on apoptotic, necroptotic or ferroptotic pathways) with all morphological and biochemical (ATP1a-dependent) features of autosis. However, we demonstrated that autosis is not dependent on the ubiquitous subunit ATP1a1 in neurons, as in dividing cell types, but on the neuronal specific ATP1a3 subunit. We also provided evidence that, in different in vitro and in vivo models where autosis is induced, ATP1a3-BECN1 interaction is increased and prevented by cardiac glycosides treatment. Interestingly, an increase in ATP1a3-BECN1 interaction is also detected in dying neurons in the autoptic brains of human newborns with severe hypoxic-ischemic encephalopathy (HIE). Altogether, these results suggest that ATP1a3-BECN1-dependent autosis could play an important role in neuronal death in HI conditions, paving the way for the development of new neuroprotective strategies in hypoxic-ischemic conditions including in severe case of human HIE.
Mots-clé
Animals, Humans, Mice, Rats, Autophagic Cell Death/drug effects, Autophagy, Hypoxia-Ischemia, Brain/metabolism, Hypoxia-Ischemia, Brain/pathology, Neurons/metabolism, Neurons/pathology, Sodium-Potassium-Exchanging ATPase/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/05/2024 14:18
Dernière modification de la notice
26/07/2024 7:02
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