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The effect of MK-801 on mTOR/p70S6K and translation-related proteins in rat frontal cortex

Cited 30 time in Web of Science Cited 32 time in Scopus
Issue Date
2008-02-12
Publisher
Elsevier
Citation
Neurosci Lett. 2008 21;434(1):23-8.
Keywords
AnimalsDizocilpine Maleate/*pharmacologyEukaryotic Initiation Factor-4E/biosynthesis/drug effects/geneticsExcitatory Amino Acid Antagonists/pharmacologyGene Expression Regulation/drug effects/physiologyGlutamic Acid/metabolismHallucinogens/pharmacologyNerve Tissue Proteins/biosynthesis/geneticsPhosphorylation/drug effectsPrefrontal Cortex/*drug effects/metabolismProtein Biosynthesis/*drug effects/geneticsProtein Kinases/biosynthesis/*drug effects/geneticsProto-Oncogene Proteins c-akt/drug effects/metabolismRNA, Messenger/drug effects/metabolismRatsRats, Sprague-DawleyReceptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolismRibosomal Protein S6 Kinases, 70-kDa/biosynthesis/*drug effects/geneticsSignal Transduction/drug effects/physiologyTranscriptional Activation/drug effects/physiologyUp-Regulation/drug effects/physiology
Abstract
In experimental animals, including rats, MK-801 produces characteristic behavioural changes that model schizophrenia. It has been hypothesized that these changes accompany long-term synaptic changes, which require protein neosynthesis. We observed the effect of MK-801 on the "mammalian target of rapamycin" (mTOR)/70-kDa ribosomal protein S6 kinase (p70S6K) pathway that regulates protein synthesis in the rat frontal cortex. A single injection of MK-801 (0.5, 1, or 2mg/kg) induced an acute increase in the phosphorylation of Akt (Ser-473) eIF4E-binding protein (4E-BP1) (Thr-37/46) and p70S6K (Thr-389). In contrast, after repeated treatment with MK-801 (1mg/kg for 5 or 10 days), the phosphorylation of Akt (Ser-473), mTOR (Ser-2481), 4E-BP1 (Thr-37/46), p70S6K (Thr-389), and S6 (Ser-240/244) increased. Thus, proteins in the mTOR/p70S6K pathway are modulated in chronic MK-801 animal models. These findings may suggest that repeated MK-801 treatment activates the signal transduction pathways involved in the initiation of protein synthesis in the rat frontal cortex.
ISSN
0304-3940 (Print)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18262357

https://hdl.handle.net/10371/63567
DOI
https://doi.org/10.1016/j.neulet.2008.01.020
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College of Medicine/School of Medicine (의과대학/대학원)Psychiatry (정신과학전공)Journal Papers (저널논문_정신과학전공)
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