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首页> 外文期刊>Toxicological sciences: An official journal of the Society of Toxicology >Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis.
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Arsenic (+ 3 oxidation state) methyltransferase and the methylation of arsenicals in the invertebrate chordate Ciona intestinalis.

机译:砷(+ 3氧化态)甲基转移酶和无脊椎动物曲线癌癌中砷的甲基化。

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Biotransformation of inorganic arsenic (iAs) involves methylation catalyzed by arsenic (+ 3 oxidation state) methyltransferase (As3mt) yielding mono-, di-, and trimethylated arsenicals. To investigate the evolution of molecular mechanisms that mediate arsenic biotransformation, a comparative genomic approach focusing on the invertebrate chordate Ciona intestinalis was used. Bioinformatic analyses identified an As3mt gene in the C. intestinalis genome. Constitutive As3mt RNA expression was observed in heart, branchial sac, and gastrointestinal tract. Adult animals were exposed to 0 or 1 ppm of iAs for 1 or 5 days. Steady-state As3mt RNA expression in the gastrointestinal tract was not modulated significantly by 5 days of exposure to iAs. Tissue levels of iAs and its methylated metabolites were determined by hydride generation-cryotrapping-gas chromatography-atomic absorption spectrometry. At either time point, exposure to iAs significantly increased concentrations of iAs and its methylated metabolites in tissues. After 5 days of exposure, total speciated arsenic concentrations were highest in branchial sac (3705 ng/g), followed by heart (1019 ng/g) and gastrointestinal tract (835 ng/g). At this time point, the sum of the speciated arsenical concentrations in gastrointestinal tract and heart equaled or exceeded that of iAs; in branchial sac, iAs was the predominant species present. Ciona intestinalis metabolizes iAs to its methylated metabolites, which are retained in tissues. This metabolic pattern is consistent with the presence of an As3mt ortholog in its genome and constitutive expression of the gene in prominent organs, making this basal chordate a useful model to examine the evolution of arsenic detoxification.
机译:无机砷(IAS)的生物转移涉及砷(+ 3氧化态)甲基转移酶(As3MT)催化的甲基化,得到单,二 - 和三甲基化砷。为了探讨介导砷生物转化的分子机制的演变,使用了聚焦在无脊椎动物曲线癌癌肠的比较基因组方法。生物信息分析鉴定了C. intestinalis基因组中的AS3MT基因。在心脏,囊囊和胃肠道中观察到组成型AS3MT RNA表达。将成年动物暴露于0或1ppm的IAS 1或5天。胃肠道中的稳态AS3MT RNA表达未明显地在暴露于IAS的5天内显着调节。通过氢化物发生 - 冷冻运动 - 气相色谱 - 原子吸收光谱法测定IAS的组织水平及其甲基化代谢物。在任一时,暴露于IAS在组织中显着增加了IAS的浓度及其甲基化代谢物。暴露5天后,在支气管囊(3705ng / g)中,总调节砷浓度最高,其次是心脏(1019 ng / g)和胃肠道(835ng / g)。在此时间点,胃肠道中所指的砷浓度和心脏等于或超过IAS的总和;在鳃囊中,IAS是存在的主要物种。 Ciona Intestinalis将IAS代谢到其甲基化代谢物中,其保留在组织中。这种代谢模式与在其基因组中的AS3MT正直的存在和突出器官中基因的组成型表达一致,使得该基础是一种有用的模型来检查砷排毒的演变。

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