The downregulation of Wnt/β-catenin signaling pathway is associated with zinc deficiency-induced proliferative deficit of C17.2 neural stem cells

The downregulation of Wnt/β-catenin signaling pathway is associated with zinc deficiency-induced... Zinc is an essential nutrient that is important for normal brain development. Zinc deficiency has been linked to aberrant neurological development and functioning. However, the molecular mechanisms underlying Zinc deficiency-induced neurological disorders remain largely elusive. In the present study, we showed that the proliferation of C17.2 neural stem cells (NSCs) was evidently impaired after exposed to low levels of Zinc chelator, N,N,N′,N′-tetrakis-(2-pyridylmethy) ethylenediamine (TPEN). In addition, we found that TPEN-induced proliferative deficit of NSCs was related with significant downregulation of Wnt/β-catenin signaling. Zinc deficiency impaired the proliferation of neural stem cells in dose- and time-dependent manners. Western blot revealed that the levels of p-Ser9-glycogensynthase kinase-3β (p-GSK-3β) and β-catenin were remarkably downregulated during TPEN-induced C17.2 proliferative impairment. Moreover, immunofluorescent analysis indicated that the level of nuclear β-catenin was apparently decreased following TPEN exposure. Furthermore, application with GSK-3β inhibitor lithium chloride (LiCl) reversed TPEN-induced downregulation of β-catenin and impairment of cell proliferation. Flow cytometry analysis also showed that TPEN-induced impairment of NSC proliferation could be reversed by LiCl. Taken together, these findings suggested that the disturbance of canonical Wnt/β-catenin signaling pathway partially accounted for Zinc deficiency-induced proliferative impairment of NSCs. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

The downregulation of Wnt/β-catenin signaling pathway is associated with zinc deficiency-induced proliferative deficit of C17.2 neural stem cells

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier B.V.
ISSN
0006-8993
D.O.I.
10.1016/j.brainres.2015.04.028
Publisher site
See Article on Publisher Site

Abstract

Zinc is an essential nutrient that is important for normal brain development. Zinc deficiency has been linked to aberrant neurological development and functioning. However, the molecular mechanisms underlying Zinc deficiency-induced neurological disorders remain largely elusive. In the present study, we showed that the proliferation of C17.2 neural stem cells (NSCs) was evidently impaired after exposed to low levels of Zinc chelator, N,N,N′,N′-tetrakis-(2-pyridylmethy) ethylenediamine (TPEN). In addition, we found that TPEN-induced proliferative deficit of NSCs was related with significant downregulation of Wnt/β-catenin signaling. Zinc deficiency impaired the proliferation of neural stem cells in dose- and time-dependent manners. Western blot revealed that the levels of p-Ser9-glycogensynthase kinase-3β (p-GSK-3β) and β-catenin were remarkably downregulated during TPEN-induced C17.2 proliferative impairment. Moreover, immunofluorescent analysis indicated that the level of nuclear β-catenin was apparently decreased following TPEN exposure. Furthermore, application with GSK-3β inhibitor lithium chloride (LiCl) reversed TPEN-induced downregulation of β-catenin and impairment of cell proliferation. Flow cytometry analysis also showed that TPEN-induced impairment of NSC proliferation could be reversed by LiCl. Taken together, these findings suggested that the disturbance of canonical Wnt/β-catenin signaling pathway partially accounted for Zinc deficiency-induced proliferative impairment of NSCs.

Journal

Brain ResearchElsevier

Published: Jul 30, 2015

References

  • Functions of zinc in signaling, proliferation and differentiation of mammalian cells
    Beyersmann, D.; Haase, H.
  • Zinc deficiency impairs neuronal precursor cell proliferation and induces apoptosis via p53-mediated mechanisms
    Corniola, R.S.; Tassabehji, N.M.; Hare, J.; Sharma, G.; Levenson, C.W.
  • Disruption of the CaMKII/CREB signaling is associated with zinc deficiency-induced learning and memory impairments
    Gao, H.L.; Xu, H.; Xin, N.; Zheng, W.; Chi, Z.H.; Wang, Z.Y.
  • Recognition of zinc-deficiency syndrome
    Prasad, A.S.
  • Aspergillus fumigatus fungaemia and myocarditis in a patient with acquired immunodeficiency syndrome
    Schonheyder, H.; Hoffmann, S.; Jensen, H.E.; Hansen, B.F.; Franzmann, M.B.
  • Enhanced excitability of hippocampal mossy fibers and CA3 neurons under dietary zinc deficiency
    Takeda, A.; Yamada, K.; Minami, A.; Nagano, T.; Oku, N.

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