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The phosphatase inhibitor, okadaic acid, strongly protects primary rat cortical neurons from lethal oxygen–glucose deprivation

Par Conseil national de recherches du Canada

DOITrouver le DOI : https://doi.org/10.1016/j.bbrc.2008.11.036
AuteurRechercher : 1; Rechercher : 1; Rechercher : 1
Affiliation
  1. Conseil national de recherches du Canada. Institut des sciences biologiques du CNRC
FormatTexte, Article
Sujet1-phosphatidylinositol 3-kinase; acid; animals; antagonists & inhibitors; Okadaic acid; IGF-1; bFGF; neuroprotection; oxygen-glucose deprivation; cortical neuron; brain; canada; cells,cultured; cerebral Cortex; cytology; cytoprotection; drug effects; enzyme; enzyme inhibitors; enzymology; glucose; inhibitor; inhibitors; metabolism; mitogen-activated protein kinase kinases; molecular; neurons; neuroprotective agents; okadaic acid; oxygen; pathway; pathways; peptide; pharmacology; phosphoric monoester hydrolases; phosphorylation; protection; protein; proteins; proto-oncogene proteins c-akt; rats; synthesis
Résumé
The protein kinase-mediated actions of peptide growth factors such as IGF-1 and bFGF protect cultured neurons from being killed by the oxygen and glucose deprivations (OGD) that prevail in the ‘stroked brain’. Here, we show that neuroprotection by IGF-1 is mediated by PI-3K/Akt, whereas that of bFGF is mediated by MAPK. IGF-1 and bFGF together did not further increase protection suggesting a downstream convergence of their pathways. Since protein kinases mediated the protection, a phosphatase inhibitor such as okadaic acid (OA) might be as protective as the growth factors against OGD. Here, we show that OA is actually a much more effective protector. It increased the phosphorylation of both PI-3K/Akt and MAPK, and stimulated new protein synthesis. OA also acted independently of the CREB activation and FKHRL1 and GSK-3 inactivation which have been implicated in IGF-1 actions.
Date de publication
Dans
  • Biochemical and Biophysical Research Communications 378, nº 3 (19 novembre 2008) : 394–398.
Langueanglais
Publications évaluées par des pairsOui
Numéro NPARC15329252
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Identificateur de l’enregistrement6a495f7b-9c39-42b9-8aaf-4fe4346fbb54
Enregistrement créé2010-05-21
Enregistrement modifié2020-04-15
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