The downregulation of Wnt/β-catenin signaling pathway is associated with zinc deficiency-induced proliferative deficit of C17.2 neural stem cells.
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.
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Jianya
J
Zhao
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Occupational Medicine and Environmental Toxicity, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Jingling
J
Han
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Occupational Medicine and Environmental Toxicity, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Junkang
J
Jiang
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Occupational Medicine and Environmental Toxicity, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Shangshi
S
Shi
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Occupational Medicine and Environmental Toxicity, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Xia
X
Ma
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Occupational Medicine and Environmental Toxicity, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Xinhang
X
Liu
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Cheng
C
Wang
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Xiaoke
X
Nie
Department of Pathology, Medical College, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Yunhua
Y
He
Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Department of Occupational Medicine and Environmental Toxicity, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China.
Shengyang
S
Jiang
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu Province, People's Republic of China. Electronic address: chwan@ntu.edu.cn.
Chunhua
C
Wan
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D005029:Ethylenediamines; D051379:Mice; D058953:Neural Stem Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D015032:Zinc / Q000172:deficiency*; D051176:beta Catenin / Q000378:metabolism
D005029:Ethylenediamines; D051176:beta Catenin; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
C17.2 cells; Neural stem cell proliferation; Wnt/β-catenin signaling; Zinc deficiency