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微囊藻毒素-LR 急性暴露通过转录乙酰胆碱酯酶激活增加斑马鱼(Danio rerio)大脑中的乙酰胆碱酯酶活性。

Microcystin-LR acute exposure increases AChE activity via transcriptional ache activation in zebrafish (Danio rerio) brain.

机构信息

Laboratório de Biologia Genômica e Molecular, Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2012 Mar;155(2):247-52. doi: 10.1016/j.cbpc.2011.09.002. Epub 2011 Sep 16.

DOI:10.1016/j.cbpc.2011.09.002
PMID:21946396
Abstract

Microcystins (MCs) constitute a family of cyanobacterial toxins, with more than 80 variants. These toxins are able to induce hepatotoxicity in several organisms mainly through the inhibition of protein phosphatases PP1 and PP2A and oxidative stress generation. Since recent evidence shows that MCs can either accumulate in brain or alter behavior patterns of fish species, in this study we tested the in vitro and in vivo effects of MC-LR at different concentrations on acetylcholinesterase (AChE) activity in zebrafish brain. In vivo studies showed that 100 μg/L MC-LR led to a significant increase in the AChE activity (27%) when zebrafish were exposed to the toxin dissolved in water, but did not cause any significant changes when injected intraperitoneally. In addition, semiquantitative RT-PCR analysis demonstrated that 100 μg/L MC-LR exposure also increased ache mRNA levels in zebrafish brain. The in vitro assays did not reveal any significant changes in AChE activity. These findings provide the first evidence that brain AChE is another potential target for MCs and suggest that the observed increases in AChE enzymatic activity and in ache transcript levels after MC-LR exposure depend, at least partially, on branchial uptake or ingestion.

摘要

微囊藻毒素(MCs)是一类蓝藻毒素,有超过 80 种变体。这些毒素主要通过抑制蛋白磷酸酶 PP1 和 PP2A 并产生氧化应激,从而在多种生物体中引起肝毒性。由于最近的证据表明 MCs 可以在大脑中积累或改变鱼类的行为模式,因此在这项研究中,我们测试了 MC-LR 在不同浓度下对斑马鱼大脑乙酰胆碱酯酶(AChE)活性的体外和体内影响。体内研究表明,当斑马鱼暴露于溶解在水中的毒素时,100μg/L 的 MC-LR 会导致 AChE 活性显著增加(27%),但当通过腹腔注射时不会引起任何显著变化。此外,半定量 RT-PCR 分析表明,100μg/L 的 MC-LR 暴露也会增加斑马鱼大脑中的 ache mRNA 水平。体外测定未显示 AChE 活性有任何显著变化。这些发现首次提供了证据,表明脑 AChE 是 MCs 的另一个潜在靶标,并表明 MC-LR 暴露后观察到的 AChE 酶活性和 ache 转录物水平的增加至少部分取决于鳃的摄取或摄入。

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