Noradrenaline enhances the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of PI3K/Akt and the mTOR/S6K pathway

Details

Serval ID
serval:BIB_BD0AAE1D5B89
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Noradrenaline enhances the expression of the neuronal monocarboxylate transporter MCT2 by translational activation via stimulation of PI3K/Akt and the mTOR/S6K pathway
Journal
Journal of Neurochemistry
Author(s)
Chenal  J., Pellerin  L.
ISSN
0022-3042 (Print)
Publication state
Published
Issued date
07/2007
Volume
102
Number
2
Pages
389-97
Notes
Journal Article
Research Support, Non-U.S. Gov't --- Old month value: Jul
Abstract
Monocarboxylate transporter 2 (MCT2) expression is up-regulated by noradrenaline (NA) in cultured cortical neurons via a putative but undetermined translational mechanism. Western blot analysis showed that p44/p42 mitogen-activated protein kinase (MAPK) was rapidly and strongly phosphorylated by NA treatment. NA also rapidly induced serine/threonine protein kinase from AKT virus (Akt) phosphorylation but to a lesser extent than p44/p42 MAPK. However, Akt activation persisted over a longer period. Similarly, NA induced a rapid and persistent phosphorylation of mammalian target of rapamycin (mTOR), a kinase implicated in the regulation of translation in the central nervous system. Consistent with activation of the mTOR/S6 kinase pathway, phosphorylation of the ribosomal S6 protein, a component of the translation machinery, could be observed upon treatment with NA. In parallel, it was found that the NA-induced increase in MCT2 protein was almost completely blocked by LY294002 (phosphoinositide 3-kinase inhibitor) as well as by rapamycin (mTOR inhibitor), while mitogen-activated protein kinase kinase and p38 MAPK inhibitors had much smaller effects. Taken together, these data reveal that NA induces an increase in neuronal MCT2 protein expression by a mechanism involving stimulation of phosphoinositide 3-kinase/Akt and translational activation via the mTOR/S6 kinase pathway. Moreover, considering the role of NA in synaptic plasticity, alterations in MCT2 expression as described in this study might represent an adaptation to face energy demands associated with enhanced synaptic transmission.
Keywords
1-Phosphatidylinositol 3-Kinase/drug effects/*metabolism Animals Brain/*metabolism Cells, Cultured Enzyme Inhibitors/pharmacology MAP Kinase Signaling System/drug effects/physiology Mice Monocarboxylic Acid Transporters/agonists/genetics/*metabolism Neuronal Plasticity/drug effects/physiology Neurons/drug effects/*metabolism Norepinephrine/pharmacology/*physiology Phosphorylation/drug effects Protein Biosynthesis/drug effects/physiology Protein Kinases/drug effects/*metabolism Proto-Oncogene Proteins c-akt/drug effects/metabolism Ribosomal Protein S6 Kinases, 90-kDa/drug effects/metabolism Signal Transduction/drug effects/*physiology Synaptic Transmission/drug effects/physiology Up-Regulation/drug effects/physiology
Pubmed
Web of science
Open Access
Yes
Create date
24/01/2008 13:17
Last modification date
20/08/2019 15:31
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