Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism
Zhipeng Qi
1
,
Shuang Wang
1
,
Jiashuo Li
1
,
Yi Wen
1
,
Rong Cui
1
,
Ke Zhang
2
,
Yanan Liu
1, 3
,
Xinxin Yang
1, 4
,
Lei Zhang
1
,
Bin Xu
1
,
Wei Liu
1
,
Zhaofa Xu
1
,
Yu Deng
1
3
Department of Preventive Health, Zhuhai People's Hospital, Zhuhai, Guangdong, China
|
4
School of Public Health, Xuzhou Medical University, Xuzhou 221004, China
|
Publication type: Journal Article
Publication date: 2022-03-01
scimago Q1
wos Q1
SJR: 3.078
CiteScore: 24.6
Impact factor: 11.3
ISSN: 03043894, 18733336
PubMed ID:
34954437
Environmental Chemistry
Environmental Engineering
Health, Toxicology and Mutagenesis
Pollution
Waste Management and Disposal
Abstract
One of the major environmental factors that induce PD is Manganese (Mn). Cellular and molecular mechanism of parkinsonism caused by Mn has not been explored clearly. The results of in vivo and in vitro experiments showed that Mn exposure caused abnormal projection of dopaminergic neurons and decreased mRNA expression and protein levels of FTO. This is due to Mn-induced the upregulation of Foxo3a. Using the cell model of overexpression of FTO, we found that FTO could antagonize Mn-induced the down-regulation of axon guidance molecule ephrin-B2 through RNA-seq, MeRIP-qPCR, and RT-qPCR experiments. Through RIP-seq and actinomycin D experiments, it was found that FTO can up-regulate the mRNA m6A level of ephrin-B2, which can be recognized by YTHDF2 and degraded. Finally, it is proved that Mn induces dopaminergic neurons projection injury and motor dysfunction through Foxo3a/FTO/m6A/ephrin-B2/YTHDF2 signal pathway.
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GOST
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Qi Z. et al. Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism // Journal of Hazardous Materials. 2022. Vol. 426. p. 128099.
GOST all authors (up to 50)
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Qi Z., Wang S., Li J., Wen Y., Cui R., Zhang K., Liu Y., Yang X., Zhang L., Xu B., Liu W., Xu Z., Deng Yu. Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism // Journal of Hazardous Materials. 2022. Vol. 426. p. 128099.
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RIS
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TY - JOUR
DO - 10.1016/j.jhazmat.2021.128099
UR - https://doi.org/10.1016/j.jhazmat.2021.128099
TI - Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism
T2 - Journal of Hazardous Materials
AU - Qi, Zhipeng
AU - Wang, Shuang
AU - Li, Jiashuo
AU - Wen, Yi
AU - Cui, Rong
AU - Zhang, Ke
AU - Liu, Yanan
AU - Yang, Xinxin
AU - Zhang, Lei
AU - Xu, Bin
AU - Liu, Wei
AU - Xu, Zhaofa
AU - Deng, Yu
PY - 2022
DA - 2022/03/01
PB - Elsevier
SP - 128099
VL - 426
PMID - 34954437
SN - 0304-3894
SN - 1873-3336
ER -
Cite this
BibTex (up to 50 authors)
Copy
@article{2022_Qi,
author = {Zhipeng Qi and Shuang Wang and Jiashuo Li and Yi Wen and Rong Cui and Ke Zhang and Yanan Liu and Xinxin Yang and Lei Zhang and Bin Xu and Wei Liu and Zhaofa Xu and Yu Deng},
title = {Protective role of mRNA demethylase FTO on axon guidance molecules of nigro-striatal projection system in manganese-induced parkinsonism},
journal = {Journal of Hazardous Materials},
year = {2022},
volume = {426},
publisher = {Elsevier},
month = {mar},
url = {https://doi.org/10.1016/j.jhazmat.2021.128099},
pages = {128099},
doi = {10.1016/j.jhazmat.2021.128099}
}