二恶英神经毒理机制研究进展
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- 英文论文题名：Advances in Understanding the Mechanism of Dioxin Neurotoxicity
- 论文作者：赵斌 ; 谢群慧 ; 徐丽 ; 徐团
- 英文论文作者：Bin Zhao ; Heidi Q.Xie ; Sherry L.Xu ; Tuan Xu ; Research Center for Eco-environmental Sciences ; Chinese Academy of Sciences
- 年：2016
- 作者机构：中国科学院生态环境研究中心;
- 论文关键词：二恶英 ; 芳香烃受体 ; 神经毒理 ; 分子机制
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十六分会：环境化学
- 语种：中文
- 分类号：R114
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十六分会 ; 环境化学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：2
- 文件大小：114k
- 原文格式：D
- 会议级别：全国
摘要
人类暴露于二恶英产生一系列毒理和健康效应,包括致癌、致畸性、内分泌干扰、组织和器官特异性毒性等,其神经毒性机理的研究一直以来是该领域的热点。乙酰胆碱酯酶(ACh E)在中枢和外周神经系统的胆碱能神经传导过程中发挥着重要的作用,然而二恶英是否能够干扰胆碱能神经传导系统一直未有相关科学证据。我们研究发现二恶英并非通过直接作用在乙酰胆碱酯酶的活性中心而是通过芳香烃受体(AHR)在转录水平上抑制神经元乙酰胆碱酯酶的活性这样一种新的机制,从而干扰到胆碱能神经传导系统。这是首次关于二恶英通过AHR及下游信号通路影响胆碱能神经传导系统的研究报道。近年来的研究发现芳香烃受体不仅在介导二恶英神经毒性作用中发挥重要的作用,在一些重要的生理过程中也扮演着关键的角色,然而迄今为止对芳香烃受体真正的生物学功能的研究和认识还非常有限,对于其深入的研究将大大促进我们对于二恶英神经毒性机理的理解。
Exposure to dioxins produce a wide variety of toxic and health effects,such as tumor promotion,teratogenicity,endocrine disruption and tissue-and organ-specific toxicities.The study of mechanism of neurotoxicity is a hot area in the past years since significant deficits in cognitive functioning have been reported in humans exposed to dioxins and dioxin-like compounds.Studies demonstrated that dioxin produced its neurotoxicity by disrupting a number of neuro-transmission systems.Acetylcholinesterase(ACh E) plays important roles in cholinergic neurotransmission in central and peripheral nervous system.While evidence suggests that dioxins induce cholinergic dysfunction mediated by hypothyroidism,little is known about direct effects of dioxins on the cholinergic system.We found a novel mechanism whereby dioxin suppressed the activity of neuronal ACh E via AHR(aryl hydrocarbon receptor) mediated transcriptional down-regulation.Apart from this transcriptional mechanism,we found no evidence showing that dioxin could inhibit ACh E activity by direct interaction with the catalytic subunit.The promoter activity,transcriptional expression as well as enzymatic activity of ACh E were examined in neuroblastoma cells and the results further support the notion that ACh E is a functional molecule sensitive to dioxin and DLCs in neurons.This is the first study to report direct interference by dioxin with the cholinergic neurotransmission system via AHR and AHR-mediated signal pathway.While,the study of the function of AHR in mediating the dioxin toxicity is the main focus in toxicity research over decades,only recently it has been observed that AHR plays important roles in normal physiological processes especially in immune balance,homeostasis and development.More extensive research and better understanding of the physiological function of AHR in neurons will enhance our understanding of broad-spectrum adverse effects induced by dioxins in the nervous system.
Exposure to dioxins produce a wide variety of toxic and health effects,such as tumor promotion,teratogenicity,endocrine disruption and tissue-and organ-specific toxicities.The study of mechanism of neurotoxicity is a hot area in the past years since significant deficits in cognitive functioning have been reported in humans exposed to dioxins and dioxin-like compounds.Studies demonstrated that dioxin produced its neurotoxicity by disrupting a number of neuro-transmission systems.Acetylcholinesterase(ACh E) plays important roles in cholinergic neurotransmission in central and peripheral nervous system.While evidence suggests that dioxins induce cholinergic dysfunction mediated by hypothyroidism,little is known about direct effects of dioxins on the cholinergic system.We found a novel mechanism whereby dioxin suppressed the activity of neuronal ACh E via AHR(aryl hydrocarbon receptor) mediated transcriptional down-regulation.Apart from this transcriptional mechanism,we found no evidence showing that dioxin could inhibit ACh E activity by direct interaction with the catalytic subunit.The promoter activity,transcriptional expression as well as enzymatic activity of ACh E were examined in neuroblastoma cells and the results further support the notion that ACh E is a functional molecule sensitive to dioxin and DLCs in neurons.This is the first study to report direct interference by dioxin with the cholinergic neurotransmission system via AHR and AHR-mediated signal pathway.While,the study of the function of AHR in mediating the dioxin toxicity is the main focus in toxicity research over decades,only recently it has been observed that AHR plays important roles in normal physiological processes especially in immune balance,homeostasis and development.More extensive research and better understanding of the physiological function of AHR in neurons will enhance our understanding of broad-spectrum adverse effects induced by dioxins in the nervous system.
引文
[1]Zhao B,Zheng M,Jiang G.Environ.Health Persp.2011,119:A112
[2]Innocentin YLS,Withers DR,Roberts NA,Gallagher AR,Grigorieva EF,Wilhelm C,Veldhoen M.Cell2011,147:629.
[3]Kiss EA,Vonarbourg C,Kopfmann S,Hobeika E,Finke D,Esser C,Diefenbach A.Science 2011,334:1561.
[4]Tian J,Feng Y,Fu H,Xie HQ,Jiang JX,Zhao B.ES&T.2015,49:9518.
[5]Xie HQ,Xu HM,Fu HL,Hu Q,Tian WJ,Pei XH,Zhao B.Environ.Health Persp.2013,121:613.
[2]Innocentin YLS,Withers DR,Roberts NA,Gallagher AR,Grigorieva EF,Wilhelm C,Veldhoen M.Cell2011,147:629.
[3]Kiss EA,Vonarbourg C,Kopfmann S,Hobeika E,Finke D,Esser C,Diefenbach A.Science 2011,334:1561.
[4]Tian J,Feng Y,Fu H,Xie HQ,Jiang JX,Zhao B.ES&T.2015,49:9518.
[5]Xie HQ,Xu HM,Fu HL,Hu Q,Tian WJ,Pei XH,Zhao B.Environ.Health Persp.2013,121:613.