L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade.

Détails

Ressource 1Télécharger: BIB_A8DA2BBFAC62.P001.pdf (1409.55 [Ko])
Etat: Public
Version: Final published version
ID Serval
serval:BIB_A8DA2BBFAC62
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade.
Périodique
Scientific Reports
Auteur(s)
Jourdain P., Allaman I., Rothenfusser K., Fiumelli H., Marquet P., Magistretti P.J.
ISSN
2045-2322 (Electronic)
ISSN-L
2045-2322
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
6
Pages
21250
Langue
anglais
Notes
Publication types: Journal ArticlePublication Status: epublish
Résumé
Converging experimental data indicate a neuroprotective action of L-Lactate. Using Digital Holographic Microscopy, we observe that transient application of glutamate (100 μM; 2 min) elicits a NMDA-dependent death in 65% of mouse cortical neurons in culture. In the presence of L-Lactate (or Pyruvate), the percentage of neuronal death decreases to 32%. UK5099, a blocker of the Mitochondrial Pyruvate Carrier, fully prevents L-Lactate-mediated neuroprotection. In addition, L-Lactate-induced neuroprotection is not only inhibited by probenicid and carbenoxolone, two blockers of ATP channel pannexins, but also abolished by apyrase, an enzyme degrading ATP, suggesting that ATP produced by the Lactate/Pyruvate pathway is released to act on purinergic receptors in an autocrine/paracrine manner. Finally, pharmacological approaches support the involvement of the P2Y receptors associated to the PI3-kinase pathway, leading to activation of KATP channels. This set of results indicates that L-Lactate acts as a signalling molecule for neuroprotection against excitotoxicity through coordinated cellular pathways involving ATP production, release and activation of a P2Y/KATP cascade.
Pubmed
Web of science
Open Access
Oui
Création de la notice
04/03/2016 16:48
Dernière modification de la notice
20/08/2019 15:13
Données d'usage