title: The effect of MK-801 on mTOR/p70S6K and translation-related proteins in rat frontal cortex.
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.
authors.affiliation: Department of Psychiatry, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Se Chang
authors.initials: SC
authors.lastname: Yoon
authors.forename: Myoung Suk
authors.initials: MS
authors.lastname: Seo
authors.forename: Se Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Won Je
authors.initials: WJ
authors.lastname: Jeon
authors.forename: Yong Min
authors.initials: YM
authors.lastname: Ahn
authors.forename: Ung Gu
authors.initials: UG
authors.lastname: Kang
authors.forename: Yong Sik
authors.initials: YS
authors.lastname: Kim
mesh_terms: D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D039561:Eukaryotic Initiation Factor-4E / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006213:Hallucinogens / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000235:genetics; D011494:Protein Kinases / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000096:biosynthesis / Q000187:drug effects* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D011494:Protein Kinases; C546845:mTOR protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases