PMID- 33120262 OWN - NLM STAT- MEDLINE DCOM- 20210107 LR - 20210107 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 208 DP - 2021 Jan 15 TI - Inflammatory lncRNA AK039862 regulates paraquat-inhibited proliferation and migration of microglial and neuronal cells through the Pafah1b1/Foxa1 pathway in co-culture environments. PG - 111424 LID - S0147-6513(20)31261-6 [pii] LID - 10.1016/j.ecoenv.2020.111424 [doi] AB - Emerging evidences having suggested that particular lncRNAs have a potential effect on PD progression through provoking damage and inflammatory responses of microglia/ dopaminergic cells. In addition, paraquat can be accumulated in human body through various approaches and have an increased risk for Parkinson's disease. However, the specific role and mechanism of lncRNA related to neurotoxic in the progression of PD is unclear. In our study, a mouse PD model was established induced by the intraperitoneal injection of paraquat (5 mg/kg and 10 mg/kg) every three days (10 times). We determined differential expression of lncRNA AK039862 and its potential targeted genes Pafah1b1/Foxa1 in PD mouse model, then we used fluorescence in situ hybridization (FISH) to visualize the cellular distribution of AK039862. Short interfering RNAs (siRNAs) and overexpression plasmids were designed for knockdown or overexpression of AK039862. To simulate the coexisting dopaminergic cells and microglia cells in vitro, we applied several non-contact co-culture models, including conditioned medium and Transwell co-culture systems. Cytotoxicity of PQ was evaluated using bv2 cells with the concentrations: 30, 60 muM, and mn9d cells with the concentrations: 50, 100 muM. As a result, we depicted multiple interesting individual and interactive features of inflammatory lncRNA AK039862 involved in PQ-induced cellular functional effects. First, we detected that AK039862 contributed to the neuronal injury process in PQ-treated mice and co-localization of AK039862 with dopaminergic cells in vivo. And interestingly, we demonstrated that PQ significantly inhibited microglia and dopaminergic cells proliferation and microglia migration in vitro. Further research indicated that the PQ-induced low expression of AK039862 rescued microglia proliferation and migration inhibition via the AK039862/Pafah1b1/Foxa1 pathway. Meanwhile, AK039862 also participated in the interaction between microglia and dopaminergic cells with PQ treatment in non-contact co-culture models. In summary, we found that PQ inhibited the proliferation and migration of microglial cells, and elucidated AK039862 played a key role in PQ-induced neuroinflammatory damage through Pafah1b1/Foxa1. Finally, inflammatory AK039862 is involved in the complex communication between microglia and dopaminergic cells in the environment of PQ damage. CI - Copyright (c) 2020 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Zhang, Yinyin AU - Zhang Y AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Nutrition and Food Hygiene, Faculty of Naval Medicine, The Second Military Medical University, Shanghai 200433, China. Electronic address: zhangyinyin2017@163.com. FAU - Shao, Wenya AU - Shao W AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: shaowenya@yeah.net. FAU - Wu, Jingwen AU - Wu J AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: Jingwen_Wu@163.com. FAU - Huang, Shouxiong AU - Huang S AD - Department of Environmental Health, College of Medicine, University of Cincinnati, Ohio 45267, United States. Electronic address: Shouxiong.huang@uc.edu. FAU - Yang, Hongyu AU - Yang H AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: gdpuyhy@163.com. FAU - Luo, Zhousong AU - Luo Z AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: 1010017587@qq.com. FAU - Zheng, Fuli AU - Zheng F AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: 416201671@qq.com. FAU - Wang, Yuan-Liang AU - Wang YL AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: wangyl@fjmu.edu.cn. FAU - Cai, Ping AU - Cai P AD - The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: caipingfjmu@163.com. FAU - Guo, Zhenkun AU - Guo Z AD - The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: guozhenkunai@163.com. FAU - Wu, Siying AU - Wu S AD - The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: fmuwsy@163.com. FAU - Li, Huangyuan AU - Li H AD - Department of Preventive Medicine, School of Public Health, Fujian Medical University, Fuzhou 350122, China; The Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350122, China; Fujian Provincial Key Laboratory of Environmental Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, China. Electronic address: fmulhy@163.com. LA - eng PT - Journal Article DEP - 20201022 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (FOXA1 protein, human) RN - 0 (Hepatocyte Nuclear Factor 3-alpha) RN - 0 (Herbicides) RN - 0 (Microtubule-Associated Proteins) RN - 0 (RNA, Long Noncoding) RN - EC 3.1.1.47 (1-Alkyl-2-acetylglycerophosphocholine Esterase) RN - EC 3.1.1.47 (PAFAH1B1 protein, human) RN - EC 3.1.1.47 (Pafah1b1 protein, mouse) RN - PLG39H7695 (Paraquat) SB - IM MH - 1-Alkyl-2-acetylglycerophosphocholine Esterase/metabolism/pharmacology MH - Animals MH - Cell Proliferation MH - Coculture Techniques MH - Disease Models, Animal MH - Dopaminergic Neurons/metabolism MH - Hepatocyte Nuclear Factor 3-alpha/metabolism/pharmacology MH - Herbicides/*toxicity MH - In Situ Hybridization, Fluorescence MH - Male MH - Mice MH - Microglia/drug effects MH - Microtubule-Associated Proteins/metabolism MH - Neurotoxicity Syndromes/metabolism MH - Paraquat/*toxicity MH - RNA, Long Noncoding/*metabolism OTO - NOTNLM OT - LncRNA OT - Neuroinflammation OT - Non-contact co-culture OT - Paraquat OT - Parkinson's disease OT - Pesticide EDAT- 2020/10/30 06:00 MHDA- 2021/01/08 06:00 CRDT- 2020/10/29 20:10 PHST- 2020/06/26 00:00 [received] PHST- 2020/09/07 00:00 [revised] PHST- 2020/09/25 00:00 [accepted] PHST- 2020/10/30 06:00 [pubmed] PHST- 2021/01/08 06:00 [medline] PHST- 2020/10/29 20:10 [entrez] AID - S0147-6513(20)31261-6 [pii] AID - 10.1016/j.ecoenv.2020.111424 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2021 Jan 15;208:111424. doi: 10.1016/j.ecoenv.2020.111424. Epub 2020 Oct 22.