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Arsenic transport by zebrafish aquaglyceroporins

机译:斑马鱼aquaglyceroporins的砷运输

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Background Arsenic is one of the most ubiquitous toxins and endangers the health of tens of millions of humans worldwide. It is a mainly a water-borne contaminant. Inorganic trivalent arsenic (AsIII) is one of the major species that exists environmentally. The transport of AsIII has been studied in microbes, plants and mammals. Members of the aquaglyceroporin family have been shown to actively conduct AsIII and its organic metabolite, monomethylarsenite (MAsIII). However, the transport of AsIII and MAsIII in in any fish species has not been characterized. Results In this study, five members of the aquaglyceroporin family from zebrafish (Danio rerio) were cloned, and their ability to transport water, glycerol, and trivalent arsenicals (AsIII and MAsIII) and antimonite (SbIII) was investigated. Genes for at least seven aquaglyceroporins have been annotated in the zebrafish genome project. Here, five genes which are close homologues to human AQP3, AQP9 and AQP10 were cloned from a zebrafish cDNA preparation. These genes were named aqp3, aqp3l, aqp9a, aqp9b and aqp10 according to their similarities to the corresponding human AQPs. Expression of aqp9a, aqp9b, aqp3, aqp3l and aqp10 in multiple zebrafish organs were examined by RT-PCR. Our results demonstrated that these aquaglyceroporins exhibited different tissue expression. They are all detected in more than one tissue. The ability of these five aquaglyceroporins to transport water, glycerol and the metalloids arsenic and antimony was examined following expression in oocytes from Xenopus leavis. Each of these channels showed substantial glycerol transport at equivalent rates. These aquaglyceroporins also facilitate uptake of inorganic AsIII, MAsIII and SbIII. Arsenic accumulation in fish larvae and in different tissues from adult zebrafish was studied following short-term arsenic exposure. The results showed that liver is the major organ of arsenic accumulation; other tissues such as gill, eye, heart, intestine muscle and skin also exhibited significant ability to accumulate arsenic. The zebrafish larvae also accumulate considerable amounts of arsenic. Conclusion This is the first molecular identification of fish arsenite transport systems and we propose that the extensive expression of the fish aquaglyceroporins and their ability to transport metalloids suggests that aquaglyceroporins are the major pathways for arsenic accumulation in a variety of zebrafish tissues. Uptake is one important step of arsenic metabolism. Our results will contribute to a new understanding of aquatic arsenic metabolism and will support the use of zebrafish as a new model system to study arsenic associated human diseases.
机译:背景技术砷是最普遍存在的毒素之一,危害着全球数千万人类的健康。它主要是水传播的污染物。无机三价砷(As III )是环境中存在的主要物种之一。已在微生物,植物和哺乳动物中研究了As III 的运输。已经证明,水甘油穿孔素家族的成员积极地进行As 及其有机代谢产物一甲基亚砷酸盐(MAs III )。但是,尚无任何鱼类中As III 和MAs III 的运输特征。结果在本研究中,克隆了斑马鱼(Danio rerio)的五水甘油通道家族成员,并具有转运水,甘油和三价砷(As III 和MAs III )和锑矿(Sb III )。斑马鱼基因组计划中已经注释了至少七个水甘油糖蛋白的基因。在此,从斑马鱼的cDNA制备物中克隆了与人AQP3,AQP9和AQP10非常相似的五个基因。这些基因根据与相应人类AQP的相似性而被命名为aqp3,aqp31,aqp9a,aqp9b和aqp10。通过RT-PCR检查aqp9a,aqp9b,aqp3,aqp31和aqp10在多个斑马鱼器官中的表达。我们的结果表明,这些水甘油糖蛋白表现出不同的组织表达。它们都在一个以上的组织中被检测到。在非洲爪蟾的卵母细胞中表达后,检查了这五个水甘油糖蛋白运输水,甘油以及准金属砷和锑的能力。这些通道中的每一个均以相当的速率显示出大量的甘油转运。这些水甘油糖蛋白还促进无机As III ,MAs III 和Sb III 的吸收。在短期接触砷后,研究了成年斑马鱼鱼幼体和不同组织中的砷积累。结果表明,肝脏是砷积累的主要器官。其他组织,例如腮,眼,心脏,肠肌肉和皮肤,也表现出显着的砷蓄积能力。斑马鱼的幼虫也积累了大量的砷。结论这是鱼亚砷酸盐转运系统的首次分子鉴定,我们提出鱼水甘油糖蛋白的广泛表达及其转运类金属的能力表明,水甘油糖蛋白是各种斑马鱼组织中砷积累的主要途径。摄取是砷代谢的重要步骤之一。我们的结果将有助于人们对水砷代谢的新认识,并将支持斑马鱼作为研究砷相关人类疾病的新模型系统。

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