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

Handle URI:
http://hdl.handle.net/10754/596851
Title:
L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade
Authors:
Jourdain, P.; Allaman, I.; Rothenfusser, K.; Fiumelli, Hubert ( 0000-0001-5136-3045 ) ; Marquet, P.; Magistretti, Pierre J. ( 0000-0002-6678-320X )
Abstract:
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.
KAUST Department:
Biological and Environmental Sciences and Engineering (BESE) Division
Citation:
L-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade 2016, 6:21250 Scientific Reports
Publisher:
Nature Publishing Group
Journal:
Scientific Reports
Issue Date:
19-Feb-2016
DOI:
10.1038/srep21250
Type:
Article
ISSN:
2045-2322
Additional Links:
http://www.nature.com/articles/srep21250
Appears in Collections:
Articles; Biological and Environmental Sciences and Engineering (BESE) Division

Full metadata record

DC FieldValue Language
dc.contributor.authorJourdain, P.en
dc.contributor.authorAllaman, I.en
dc.contributor.authorRothenfusser, K.en
dc.contributor.authorFiumelli, Huberten
dc.contributor.authorMarquet, P.en
dc.contributor.authorMagistretti, Pierre J.en
dc.date.accessioned2016-02-21T10:25:03Zen
dc.date.available2016-02-21T10:25:03Zen
dc.date.issued2016-02-19en
dc.identifier.citationL-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascade 2016, 6:21250 Scientific Reportsen
dc.identifier.issn2045-2322en
dc.identifier.doi10.1038/srep21250en
dc.identifier.urihttp://hdl.handle.net/10754/596851en
dc.description.abstractConverging 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.en
dc.language.isoenen
dc.publisherNature Publishing Groupen
dc.relation.urlhttp://www.nature.com/articles/srep21250en
dc.rightsThis work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/en
dc.titleL-Lactate protects neurons against excitotoxicity: implication of an ATP-mediated signaling cascadeen
dc.typeArticleen
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Divisionen
dc.identifier.journalScientific Reportsen
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionBrain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerlanden
dc.contributor.institutionCentre de Neurosciences Psychiatriques, CHUV, Département de Psychiatrie, Site de Cery, CH-1008 Prilly/Lausanne, Switzerlanden
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorFiumelli, Huberten
kaust.authorMagistretti, Pierre J.en
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