Neuroglobin Regulates Wnt/ß-Catenin and NFκB Signaling Pathway through Dvl1.
Int J Mol Sci
; 19(7)2018 Jul 23.
Article
in En
| MEDLINE
| ID: mdl-30041403
ABSTRACT
Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/ß-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/ß-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of ß-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/ß-Catenin and NFκB signaling pathway through regulating Dishevelled-1.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Globins
/
Wnt Signaling Pathway
/
Nerve Tissue Proteins
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2018
Type:
Article
Affiliation country:
China