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Transcriptomic and proteomic responses of human renal HEK293 cells to uranium toxicity.
Proteomics ( IF 3.4 ) Pub Date : 2005-01-27 , DOI: 10.1002/pmic.200400896
Odette Prat 1 , Frédéric Berenguer , Véronique Malard , Emmanuelle Tavan , Nicole Sage , Gérard Steinmetz , Eric Quemeneur
Affiliation  

The industrial use of uranium, in particular depleted uranium, has pin-pointed the need to review its chemical impact on human health. Global methodologies, applied to the field of toxicology, have demonstrated their applicability to investigation of fine molecular mechanisms. This report illustrate the power of toxicogenomics to evaluate the involvement of certain genes or proteins in response to uranium. We particularly show that 25% of modulated genes concern signal transduction and trafficking, that the calcium pathway is heavily disturbed and that nephroblastomas-related genes are involved (WIT-1, STMN1, and STMN2). A set of 18 genes was deregulated whatever the concentration of toxicant, which could constitute a signature of uranium exposure. Moreover, a group of downregulated genes, with corresponding disappearing proteins (HSP90, 14-3-3 protein, HMGB1) in two-dimensional polyacrylamide gel electrophoresis (2-D PAGE), are good candidates for use as biomarkers of uranium effects. These results reveal a cross-checking between transcriptomic and proteomic technologies. Moreover, our temporal gene expression profiles suggest the existence of a concentration threshold between adaptive response and severe cell deregulation. Our results confirm the involvement of genes already described and also provide new highlights on cellular response to uranium.

中文翻译:

人肾HEK293细胞对铀毒性的转录和蛋白质组反应。

铀,特别是贫铀的工业用途,明确指出需要审查其对人类健康的化学影响。应用于毒理学领域的全球方法论已证明其可用于精细分子机理的研究。该报告说明了毒理基因组学评估某些基因或蛋白质对铀的反应的能力。我们特别表明,有25%的调节基因与信号转导和运输有关,钙通路受到严重干扰,涉及成神经细胞母细胞瘤相关基因(WIT-1,STMN1和STMN2)。无论有毒物质的浓度如何,一组18个基因都被解除管制,这可能构成铀暴露的标志。此外,还有一组下调的基因以及相应的消失蛋白(HSP90,二维聚丙烯酰胺凝胶电泳(2-D PAGE)中的14-3-3蛋白HMGB1是用作铀效应生物标志物的良好候选物。这些结果揭示了转录组学和蛋白质组学技术之间的交叉检查。此外,我们的时间基因表达谱表明在适应性反应和严重的细胞失调之间存在浓度阈值。我们的结果证实了已经描述的基因的参与,也为细胞对铀的反应提供了新的亮点。我们的时间基因表达谱表明在适应性反应和严重的细胞失调之间存在浓度阈值。我们的结果证实了已经描述的基因的参与,也为细胞对铀的反应提供了新的亮点。我们的时间基因表达谱表明在适应性反应和严重的细胞失调之间存在浓度阈值。我们的结果证实了已经描述的基因的参与,也为细胞对铀的反应提供了新的亮点。
更新日期:2019-11-01
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