TITLE:
Nerve Growth Factor Enhances Tau Isoform Expression and Transcription in IMR32 Cells
AUTHORS:
Cheryl L. Cragg, Bettina E. Kalisch
KEYWORDS:
Nerve Growth Factor (NGF), Tau, Signal Transduction, Transcription, Nitric Oxide (NO), IMR32 Cells, PC12 Cells
JOURNAL NAME:
Neuroscience and Medicine,
Vol.5 No.2,
April
30,
2014
ABSTRACT: The present study characterized the nerve growth factor (NGF)-mediated
regulation of tau protein expression and transcription in IMR32 human
neuroblastoma cells. Treatment of IMR32 cells with 50 ng/mL NGF resulted in
increased levels of specific tau protein isoforms. A 550 bp fragment of the tau
promoter was cloned and treatment of transfected IMR32 and PC12 cells with NGF
also resulted in increased promoter activation, suggesting that the
NGF-mediated increase in tau isoforms is regulated, at least in part, at the
level of transcription. Pretreatment with the MAP kinase inhibitor U0126 or the
PKC inhibitor bisindolylmaleimide 1 (BIS-1) attenuated the NGF-mediated
increase in tau transcription, indicating that the NGF-mediated activation of
the MAP kinase and PKC signaling pathways modulate tau transcription.
Pre-treatment of cells with the Akt inhibitor, LY294002 or with NOS inhibitors
Nω-nitro-L-arginine
methylester (L-NAME) or s-methylisothiourea (S-MIU) had no effect on the
NGF-mediated increase in tau promoter activation, suggesting that NO and the
NGF-Akt signaling pathway do not modulate tau transcription. Taken together,
these data demonstrate that NGF increases the levels of multiple human tau
isoforms in IMR32 cells which may result, at least in part, from NGF-mediated
PKC and MAP kinase-induced tau transcription.