Acrylamide-responsive genes in the nematode Caenorhabditis elegans
Acrylamide-responsive genes in the nematode Caenorhabditis elegans
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DOI：
10.1093/toxsci/kfm276
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发表时间：
2008-02-01
影响因子：
3.8
通讯作者：
Miwa, Johji
中科院分区：
文献类型：
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作者：
Hasegawa, Koichi;Miwa, Satsuki;Miwa, Johji
由于丙烯酰胺是一种已知的对许多动物的神经毒素和对人类的潜在致癌物，当瑞典国家食品局和斯德哥尔摩大学在2002年报告说它是在油炸或烘焙食物时形成的时，人们感到惊讶。我们在这里报告基因组和蛋白质组学分析的基因和蛋白质的秀丽隐杆线虫暴露于500毫克/升丙烯酰胺。在21，120个基因中，409个基因表达上调超过两倍，111个基因表达下调。上调的基因包括许多编码解毒酶，如谷胱甘肽S-转移酶（GST），尿苷二磷酸-葡萄糖醛酸/葡萄糖基转移酶，短链型脱氢酶，但只有一个细胞色素P450。随后的蛋白质组学分析证实了GST的严重参与。由于它们的高表达水平和丙烯酰胺代谢的核心作用，我们分析了8个GST基因的体内表达模式。虽然所有的基因都编码GST，并且在丙烯酰胺处理后表达上调了两倍以上，但它们的表达模式是不同的，并且它们的调节涉及转录因子SKN-1（一种C。核因子E2相关因子1和2的elegans同源物）。然后我们选择gst-4：：gfp转化的C.研究丙烯酰胺及其代谢产物甘氨酰亚胺在活体动物体内的解毒率。这种动物检测丙烯酰胺作为绿色荧光蛋白（GFP）的表达信号，在剂量和时间依赖性的方式，并可能被证明是一个有用的工具，不仅用于快速和廉价地检测丙烯酰胺，食品中的有害物质，但也用于分析GST诱导丙烯酰胺和其他诱导剂，如氧化应激的机制。关键词：外源性物质; II相酶;生物标志物;食品安全;毒理基因组学;蛋白质组学。
As acrylamide is a known neurotoxin for many animals and potential carcinogen for humans, it came as a surprise when the Swedish National Food Agency and Stockholm University reported in 2002 that it is formed during the frying or baking of foods. We report here genomic and proteomic analyses on genes and proteins of Caenorhabditis elegans exposed to 500 mg/l acrylamide. Of the 21,120 genes profiled, 409 genes were more than twofold upregulated and 111 genes were downregulated. Upregulated genes included many that encode detoxification enzymes such as glutathione S-transferases (GSTs), uridine diphosphate-glucuronosyl/ glucosyl transferases, and short-chain type dehydrogenases but only one cytochrome P450. Subsequent proteomic analysis confirmed the heavy involvement of GSTs. Because of their high expression levels and central roles in acrylamide metabolism, we analyzed the in vivo expression patterns of eight gst genes. Although all encoded GST and were more than twofold upregulated by acrylamide treatment, their expression patterns were varied, and their regulation involved the transcription factor SKN-1 (a C. elegans homolog of Nuclear factor E2-related factors 1 and 2). We then selected the gst-4:: gfp-transformed C. elegans to study the detoxification rate of acrylamide and its metabolite glycidimide in living animals. This animal detects acrylamide as a green fluorescence protein (GFP) expression signal in a dose- and time-dependent manner and may prove to be a useful tool not only for rapidly and inexpensively detecting acrylamide, a harmful substance in food, but also for analyzing mechanisms of GST induction by acrylamide and other inducers like oxidative stresses. Key Words: xenobiotics; Phase II enzymes; biomarkers; food safety; toxicogenomics; proteomics.