New perspective on the regulation of acetylcholinesterase via the aryl hydrocarbon receptor. Issue 6 (20th December 2020)

• Record Type: Journal Article
• Authors: Xie, Heidi Qunhui; Ma, Yongchao; Fu, Hualing; Xu, Tuan; Luo, Yali; Liu, Yiyun; Chen, Yangsheng; Xu, Li; Xia, Yingjie; Zhao, Bin
• Is Part Of: Journal of neurochemistry. Volume 158:Issue 6(2021)
• Page Start: 1254
• Page End: 1262
• Publication Date: 2020-12-20
• Subjects: acetylcholinesterase -- aryl hydrocarbon receptor -- dioxin -- dioxin‐response element -- microRNA -- neurodevelopment; Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.15261
• Languages: English
• ISSNs: 0022-3042

Abstract

Abstract: Acetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in‐depth understanding of the effects of dioxin on AChE and the related mechanisms of action might help to shed light on the molecular bases of dioxin impacts on the nervous system. In the past decade, the effects of dioxins on AChE have been revealed in cultured cells of different origins and in rodent animal models. Unlike OP and carbamate pesticides, dioxin‐induced AChE disturbance is not due to direct inhibition of enzymatic activity; instead, dioxin causes alterations of AChE expression in certain models. As a widely accepted mechanism for most dioxin effects, the aryl hydrocarbon receptor (AhR)‐dependent pathway has become a research focus in studies on the mechanism of action of dioxin‐induced AChE dysregulation. In this mini‐review, the effects of dioxin on AChE and the diverse roles of the AhR pathway in AChE regulation are summarized. Additionally, the involvement of AhR in AChE regulation during different neurodevelopmental processes is discussed. These AhR‐related findings might also provide new insight into AChE regulation triggered by diverse xenobiotics capable of interacting with AhR. Abstract : Dioxins are newly identified AChE disruptors. TCDD, a representative of this group of compounds, suppresses AChE activity via disrupting its expression in cultured neuron and muscle and the mouse brain with maternal TCDD exposure. AhR‐dependent pathway plays diverse roles in the suppression of AChE by TCDD. In human‐derived neuroblastoma cells, AhR mediates transcriptional and posttranscriptional regulations of AChE triggered by TCDD. While in rodent‐derived models, AhR‐independent mechanisms may be involved in TCDD‐induced dysregulation of AChE. A discrepancy of DRE sites on human and rodent ACHE promoters might lead to the species specific roles of AhR pathway in the regulation of AChE.