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Modification of Wnt signaling pathway on paraquat-induced inhibition of neural progenitor cell proliferation.
Food Chem Toxicol. 2018 Nov; 121:311-325.FC

Abstract

Paraquat (PQ) is an agricultural chemical used worldwide. As a potential neurotoxicant, PQ adversely affects neurogenesis and inhibits proliferation of neural progenitor cells (NPCs). However, the molecular mechanistic insights of PQ exposure on NPCs remains to be determined. Herein, we determine the extent to which Wnt/β-catenin signaling involved in the inhibition effect of PQ on mouse NPCs from subventricular zone (SVZ). NPCs were treated with different concentrations of PQ (40, 80, and 120 μM). PQ exposure provoked oxidative stress and apoptosis and PQ inhibited cell viability and proliferation in a concentration-dependent manner. Significantly, PQ exposure altered the expression/protein levels of the Wnt pathway genes in NPCs. In addition, PQ reduced cellular β-catenin, p-GSK-3β, and cyclin-D1 and increased the radio of Bax/Bcl2. Further, Wnt pathway activation by treatment with LiCl and Wnt1 attenuated PQ-induced inhibition of mNPCs proliferation. Antioxidant (NAC) treatment alleviated the inhibition of PQ-induced Wnt signaling pathway. Overall, our results suggest significant inhibitory effects of PQ on NPCs proliferation via the Wnt/β-catenin signaling pathway. Interestingly, our results implied that activation of Wnt/β-catenin signaling pathway attenuated PQ-induced autophagic cell death. Our results therefore bring our understanding of the molecular mechanisms of PQ-induced neurotoxicity.

Authors+Show Affiliations

School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.Department of Environmental Health & Engineering, Bloomberg School of Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, 21205, USA.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China.School of Public Health and Key Laboratory of Public Health Safety of the Ministry of Education, Fudan University, Shanghai, 200032, China. Electronic address: xlchang@fudan.edu.cn.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30171970

Citation

Zhao, Lina, et al. "Modification of Wnt Signaling Pathway On Paraquat-induced Inhibition of Neural Progenitor Cell Proliferation." Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, vol. 121, 2018, pp. 311-325.
Zhao L, Yan M, Wang X, et al. Modification of Wnt signaling pathway on paraquat-induced inhibition of neural progenitor cell proliferation. Food Chem Toxicol. 2018;121:311-325.
Zhao, L., Yan, M., Wang, X., Xiong, G., Wu, C., Wang, Z., Zhou, Z., & Chang, X. (2018). Modification of Wnt signaling pathway on paraquat-induced inhibition of neural progenitor cell proliferation. Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association, 121, 311-325. https://doi.org/10.1016/j.fct.2018.08.064
Zhao L, et al. Modification of Wnt Signaling Pathway On Paraquat-induced Inhibition of Neural Progenitor Cell Proliferation. Food Chem Toxicol. 2018;121:311-325. PubMed PMID: 30171970.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modification of Wnt signaling pathway on paraquat-induced inhibition of neural progenitor cell proliferation. AU - Zhao,Lina, AU - Yan,Mengling, AU - Wang,Xinjin, AU - Xiong,Guiya, AU - Wu,Chunhua, AU - Wang,Zhibin, AU - Zhou,Zhijun, AU - Chang,Xiuli, Y1 - 2018/08/30/ PY - 2018/04/11/received PY - 2018/08/16/revised PY - 2018/08/27/accepted PY - 2018/9/2/pubmed PY - 2018/11/14/medline PY - 2018/9/2/entrez KW - Apoptosis KW - Autophagic cell death KW - Neural progenitor cells KW - Paraquat KW - Proliferation inhibition KW - Wnt/β-catenin signaling pathway SP - 311 EP - 325 JF - Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association JO - Food Chem. Toxicol. VL - 121 N2 - Paraquat (PQ) is an agricultural chemical used worldwide. As a potential neurotoxicant, PQ adversely affects neurogenesis and inhibits proliferation of neural progenitor cells (NPCs). However, the molecular mechanistic insights of PQ exposure on NPCs remains to be determined. Herein, we determine the extent to which Wnt/β-catenin signaling involved in the inhibition effect of PQ on mouse NPCs from subventricular zone (SVZ). NPCs were treated with different concentrations of PQ (40, 80, and 120 μM). PQ exposure provoked oxidative stress and apoptosis and PQ inhibited cell viability and proliferation in a concentration-dependent manner. Significantly, PQ exposure altered the expression/protein levels of the Wnt pathway genes in NPCs. In addition, PQ reduced cellular β-catenin, p-GSK-3β, and cyclin-D1 and increased the radio of Bax/Bcl2. Further, Wnt pathway activation by treatment with LiCl and Wnt1 attenuated PQ-induced inhibition of mNPCs proliferation. Antioxidant (NAC) treatment alleviated the inhibition of PQ-induced Wnt signaling pathway. Overall, our results suggest significant inhibitory effects of PQ on NPCs proliferation via the Wnt/β-catenin signaling pathway. Interestingly, our results implied that activation of Wnt/β-catenin signaling pathway attenuated PQ-induced autophagic cell death. Our results therefore bring our understanding of the molecular mechanisms of PQ-induced neurotoxicity. SN - 1873-6351 UR - https://www.unboundmedicine.com/medline/citation/30171970/Modification_of_Wnt_signaling_pathway_on_paraquat_induced_inhibition_of_neural_progenitor_cell_proliferation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0278-6915(18)30621-5 DB - PRIME DP - Unbound Medicine ER -