Map kinase and PKC signaling pathways modulate NGF-mediated apoE transcription.
Neurosci Lett
; 595: 54-9, 2015 May 19.
Article
in En
| 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoproteins E
/
Protein Kinase C
/
Mitogen-Activated Protein Kinases
/
Nerve Growth Factor
Limits:
Animals
Language:
En
Journal:
Neurosci Lett
Year:
2015
Document type:
Article
Affiliation country: