Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1

• Published in: International journal of molecular sciences 2018-07, Vol.19 (7), p.2133
• Main Authors: Xun, Yu, Li, Zhen, Tang, Yingxin, Yang, Manjun, Long, Shengwen, Shu, Pan, Li, Jiabing, Xiao, Ye, Tang, Fen, Wei, Chenxi, Liu, Ning, Xiang, Shuanglin
• Format: Article
• Language: English
• Subjects: Apoptosis; Biodegradation; Cell division; Dishevelled protein; Dvl1; Ectopic expression; Immunoprecipitation; Ischemia; Kinases; Localization; Neurogenesis; Neuroglobin; Neuroprotection; Neuroprotective agents; NF-κB protein; NFκB; Ngb; Nuclei (cytology); Polyclonal antibodies; Proteasomes; Proteins; Rodents; Signal transduction; SK-N-SH; Stem cells; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Wnt protein; Wnt/β-Catenin; Yeast; β-Catenin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19072133

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/β-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/β-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 β-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/β-Catenin and NFκB signaling pathway through regulating Dishevelled-1.