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Tytuł:
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Neuroglobin Regulates Wnt/β-Catenin and NFκB Signaling Pathway through Dvl1.
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Autorzy:
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Xun, Yu
Li, Zhen
Tang, Yingxin
Yang, Manjun
Long, Shengwen
Shu, Pan
Li, Jiabing
Xiao, Ye
Tang, Fen
Wei, Chenxi
Xiang, Shuanglin
Liu, Ning
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Temat:
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PROTEINS
NEURONS
ISCHEMIA
MITOCHONDRIA
CYTOSKELETON
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Źródło:
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International Journal of Molecular Sciences; Jul2018, Vol. 19 Issue 7, p2133, 1p, 1 Diagram, 1 Chart, 4 Graphs
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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. [ABSTRACT FROM AUTHOR]
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