Glycine triggers a non-ionotropic activity of GluN2A-containing NMDA receptors to confer neuroprotection
Autor: | Zhi-Qiang Li, Mingxia Liao, Juan Chen, Yu Wan, Qi Wan, Fang Liu, Hua Feng, Brendan Lujan, Mi Zhang, Ze-Fen Wang, Rui-Xue Lei, Rong Hu |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Agonist medicine.drug_class Glycine Nerve Tissue Proteins Pharmacology Neuroprotection Receptors N-Methyl-D-Aspartate Article 03 medical and health sciences Mice 0302 clinical medicine medicine Animals Humans Glycine receptor Protein kinase B Cells Cultured Cerebral Cortex Neurons Multidisciplinary Binding Sites Chemistry Glutamate receptor 030104 developmental biology HEK293 Cells NMDA receptor Female Proto-Oncogene Proteins c-akt 030217 neurology & neurosurgery Ionotropic effect |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Ionotropic activation of NMDA receptors (NMDARs) requires agonist glutamate and co-agonist glycine. Here we show that glycine enhances the activation of cell survival-promoting kinase Akt in cultured cortical neurons in which both the channel activity of NMDARs and the glycine receptors are pre-inhibited. The effect of glycine is reduced by shRNA-mediated knockdown of GluN2A subunit-containing NMDARs (GluN2ARs), suggesting that a non-ionotropic activity of GluN2ARs mediates glycine-induced Akt activation. In support of this finding, glycine enhances Akt activation in HEK293 cells over-expressing GluN2ARs. The effect of glycine on Akt activation is sensitive to the antagonist of glycine-GluN1 binding site. As a functional consequence, glycine protects against excitotoxicity-induced neuronal death through the non-ionotropic activity of GluN2ARs and the neuroprotective effect is attenuated by Akt inhibition. Thus, this study reveals an unexpected role of glycine in eliciting a non-ionotropic activity of GluN2ARs to confer neuroprotection via Akt activation. |
Databáze: | OpenAIRE |
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