Map kinase and PKC signaling pathways modulate NGF-mediated apoE transcription
| Autor: | Megan R. Strachan-Whaley, Kate Reilly, Bettina E. Kalisch, James G. Dobson |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Apolipoprotein E
Bisindolylmaleimide Indoles Transcription Genetic Morpholines Nitric Oxide Synthase Type II Biology PC12 Cells Maleimides chemistry.chemical_compound Apolipoproteins E Nerve Growth Factor Animals LY294002 Luciferase Estrenes Promoter Regions Genetic Protein kinase C Protein Kinase C General Neuroscience Molecular biology LRP1 Pyrrolidinones Rats Nerve growth factor NG-Nitroarginine Methyl Ester nervous system chemistry Chromones Type C Phospholipases Signal transduction Mitogen-Activated Protein Kinases Proto-Oncogene Proteins c-akt Isothiuronium Signal Transduction |
| Zdroj: | Neuroscience letters. 595 |
| ISSN: | 1872-7972 |
| Popis: | 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(ɷ)-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. |
| Databáze: | OpenAIRE |
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