Wnt1 silencing enhances neurotoxicity induced by paraquat and maneb in SH-SY5Y cells

Cui Huang; Jing Ma; Bai-Xiang Li; Yan Sun

doi:10.3892/etm.2019.7963

Wnt1 silencing enhances neurotoxicity induced by paraquat and maneb in SH-SY5Y cells

Exp Ther Med. 2019 Nov;18(5):3643-3649. doi: 10.3892/etm.2019.7963. Epub 2019 Aug 30.

Authors

Cui Huang^{1

2}, Jing Ma¹, Bai-Xiang Li¹, Yan Sun¹

Affiliations

¹ Department of Toxicology, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.
² Safety and Quality Institute of Agricultural Products, Heilongjiang Academy of Agricultural Sciences, Harbin, Heilongjiang 150086, P.R. China.

Abstract

Wingless (Wnt) signaling regulates the proliferation and differentiation of midbrain dopamine (DA) neurons. Paraquat (PQ) and maneb (MB) are environmental pollutants that can be used to model Parkinson's disease (PD) in rodents. A previous study demonstrated that developmental exposure to PQ and MB affects the expression of Wnt1, Wnt5a, nuclear receptor-related factor 1 (NURR1) and tyrosine hydroxylase (TH). However, how Wnt signaling regulates these developmental factors in vitro is yet to be determined. To explore this, SH-SY5Y cells were exposed to PQ and MB. The results of the current study indicated that exposure to PQ and MB decreased Wnt1, β-catenin, NURR1 and TH levels and increased Wnt5a levels. Furthermore, Wnt1 silencing has the same effect as exposure to PQ and MB. Additionally, the neurotoxicity induced by PQ and MB is more severe in siWnt1-SH-SY5Y cells compared with normal SH-SY5Y cells. Therefore, Wnt1 may serve an important role in regulating developmental DA factors, and may be a candidate gene for PD diagnosis or gene therapy.

Keywords: Parkinson's disease; SH-SY5Y; maneb; paraquat; wingless.