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Neurosci Lett ; 595: 54-9, 2015 May 19.
Article in English | MEDLINE | ID: mdl-25797400

ABSTRACT

The present study assessed the mechanisms by which nerve growth factor (NGF) increased the level of apolipoprotein E (apoE) in PC12 cells. NGF (50ng/mL) significantly increased apoE protein levels following 72h of treatment. Similarly NGF increased luciferase activity in cells transfected with a luciferase reporter construct containing a 500bp fragment of the apoE promoter, indicating NGF-induced apoE expression is regulated, at least in part, at the level of transcription. The non-selective nitric oxide synthase (NOS) inhibitor N(É·)-nitro-L-arginine methylester (L-NAME; 20mM) did not attenuate the NGF-mediated increase in luciferase activity, while the inducible NOS inhibitor s-methylisothiourea (S-MIU; 2mM) partially attenuated this action of NGF. Inhibition of MAP kinase activation with 50µM U0126 or pre-treatment with the PKC inhibitor bisindolylmaleimide 1 (BIS-1; 10µM) prevented the NGF-mediated activation of the apoE promoter. Pre-treatment with the phospholipase C (PLC) inhibitor U73122 (5µM) partially inhibited the NGF-induced increase in luciferase activity while the Akt inhibitor LY294002 (10µM) had no effect. These data suggest NGF-induced apoE transcription requires MAP kinase and PKC activation and that these TrkA signaling pathways may be modulated by NO.


Subject(s)
Apolipoproteins E/genetics , Mitogen-Activated Protein Kinases/metabolism , Nerve Growth Factor/metabolism , Protein Kinase C/metabolism , Animals , Apolipoproteins E/metabolism , Chromones/pharmacology , Estrenes/pharmacology , Indoles/pharmacology , Isothiuronium/analogs & derivatives , Isothiuronium/pharmacology , Maleimides/pharmacology , Morpholines/pharmacology , NG-Nitroarginine Methyl Ester/pharmacology , Nerve Growth Factor/pharmacology , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/metabolism , PC12 Cells , Promoter Regions, Genetic , Protein Kinase C/antagonists & inhibitors , Proto-Oncogene Proteins c-akt/antagonists & inhibitors , Pyrrolidinones/pharmacology , Rats , Signal Transduction , Transcription, Genetic , Type C Phospholipases/antagonists & inhibitors
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