Dioxin and dioxin-like compounds suppress acetylcholinesterase activity via transcriptional downregulations in vitro.
Recently, acetylcholinesterase (AChE, EC 3.1.1.7) has received increased attention in the field of environmental sciences. Evaluation of the effects of environmental contaminants on AChE enzymatic activity not only can reflect, to some extent, the interference with the nervous system, but also can be used for monitoring pollution. Our previous study showed that 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) suppressed neuronal AChE enzymatic activity via transcriptional downregulations mediated by aryl hydrocarbon receptor. In the present study, the effects of several other dioxin-like compounds (DLCs) on neuronal AChE activity were determined, including 1,2,3,7,8-pentachlorodibenzo-p-dioxin, 2,3,7,8-tetrachlorodibenzofuran, 2,3,4,7,8-pentachlorodibenzofuran, and 2,3,7,8-tetrabromodibenzo-p-dioxin. The results showed that the enzymatic activity of AChE was significantly decreased by approximately 15-30 % after exposure to a certain concentrations of the DLCs, whereas incubating neuronal cell lysates directly with these DLCs did not inhibit AChE enzyme. Subsequent molecular mechanism study showed that these chemicals could decrease ACHE promoter activity, as well as AChE T mRNA expression, thereby suggesting the involvements of transcriptional regulation in these effects. These findings on DLCs are similar with those on 2,3,7,8-TCDD, pointing to the possibility that exposure to dioxin and DLCs, which frequently coexist in the contaminated environments, may concurrently interfere with the cholinergic functions via AChE.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, 100085, China.
Hai-Ming
HM
Xu
Heidi Qunhui
HQ
Xie
Wu-Qun
WQ
Tao
Zhi-Guang
ZG
Zhou
Shuai-Zhang
SZ
Li
Bin
B
Zhao
D000110:Acetylcholinesterase / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000031:analogs & derivatives / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D000110:Acetylcholinesterase