Effect of cadmium on glutathione S-transferase and metallothionein gene expression in coho salmon liver, gill and olfactory tissues.
Effect of cadmium on glutathione S-transferase and metallothionein gene expression in coho salmon liver, gill and olfactory tissues.
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DOI：
10.1016/j.aquatox.2011.12.012
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Gallagher EP
中科院分区：
文献类型：
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作者：
Espinoza HM;Williams CR;Gallagher EP
谷胱甘肽S-转移酶（GST）是一个多功能的第二阶段酶家族，可以解毒各种环境化学物质，反应中间体和氧化损伤的次级产物。GST mRNA表达和催化活性已被用作暴露于环境化学品的生物标志物。然而，因素，如物种差异的诱导，多个GST异构体的部分分析，以及缺乏对鱼类GST基因调控的了解，混淆了使用GST作为污染物暴露的标志物。在本研究中，我们研究了暴露于镉（Cd），一个典型的环境污染物和哺乳动物GST的诱导剂，对银鲑（Oncorhynchus kisutch）的肝脏，鳃，和嗅觉组织GST mRNA表达的影响。GST表达数据进行了比较，金属硫蛋白（MT），金属暴露的原型生物标志物。对基因组数据库的数据挖掘导致开发了针对鲑鱼GST同种型的定量实时PCR（qPCR）测定，所述同种型包括9个亚家族，包括α、μ、π、θ、ω、κ、ρ、ζ和微粒体GST。在体内急性（8-48小时）暴露于低（3.7 ppb）和高（347 ppb）水平的镉相关的环境情景引起了各种短暂的，虽然轻微的变化（<2.5倍），在组织GST的档案，包括GST mRNA表达的一些减少。在一般情况下，嗅觉GST是最早响应镉，而在嗅觉和鳃GST的表达更明显的影响，观察到在48小时相对于较早的时间点。虽然GST的评价反映了镉相关的氧化应激反应，有没有明确的GST亚型在任何组织，可以作为一个可靠的生物标志物急性镉暴露。相比之下，金属硫蛋白（MT）mRNA的一致性和显着诱导在所有三个组织中的镉，和检查的组织中，嗅觉MT是最敏感的标记镉暴露。总之，银鲑表现出复杂的GST组织概况，包括至少9种亚型，所有这些都存在于外周嗅觉系统。短期暴露于镉的环境水平会导致鲑鱼GST与氧化应激一致的短暂变化，在某些情况下，包括GST的损失。然而，在生物标志物的背景下，监测组织MT mRNA的表达，特别是在外周嗅觉系统，可能是更大的效用评估短期环境暴露镉。
The glutathione S-transferases (GSTs) are a multifunctional family of phase II enzymes that detoxify a variety of environmental chemicals, reactive intermediates, and secondary products of oxidative damage. GST mRNA expression and catalytic activity have been used as biomarkers of exposure to environmental chemicals. However, factors such as species differences in induction, partial analyses of multiple GST isoforms, and lack of understanding of fish GST gene regulation, have confounded the use of GST as markers of pollutant exposure. In the present study, we examined the effect of exposure to cadmium (Cd), a prototypical environmental contaminant and inducer of mammalian GST, on GST mRNA expression in coho salmon (Oncorhynchus kisutch) liver, gill, and olfactory tissues. GST expression data were compared to those for metallothionein (MT), a prototypical biomarker of metal exposure. Data mining of genomic databases led to the development of quantitative real-time PCR (qPCR) assays for salmon GST isoforms encompassing 9 subfamilies, including alpha, mu, pi, theta, omega, kappa, rho, zeta and microsomal GST. In vivo acute (8-48 hr) exposures to low (3.7 ppb) and high (347 ppb) levels of Cd relevant to environmental scenarios elicited a variety of transient, albeit minor changes (<2.5-fold) in tissue GST profiles, including some reductions in GST mRNA expression. In general, olfactory GSTs were the earliest to respond to cadmium, whereas, more pronounced effects in olfactory and gill GST expression were observed at 48 hr relative to earlier time points. Although evaluation of GSTs reflected a cadmium-associated oxidative stress response, there was no clear GST isoform in any tissue that could serve as a reliable biomarker of acute cadmium exposure. By contrast, metallothionein (MT) mRNA was consistently and markedly induced in all three tissues by cadmium, and among the tissues examined, olfactory MT was the most sensitive marker of cadmium exposures. In summary, coho salmon exhibit a complex GST tissue profile consisting of at least 9 isoforms, all of which are present in the peripheral olfactory system. Short-term exposure to environmental levels of Cd causes transient changes in salmon GST consistent with oxidative stress, and in some cases, includes a loss of GST. In a biomarker context, however, monitoring of tissue MT mRNA expression, especially in the peripheral olfactory system, may be of greater utility for assessing short-term environmental exposures to cadmium.