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Proteomic and transcriptomic changes in rat liver following oral feeding of formaldehyde

机译:口服喂食甲醛后大鼠肝脏的蛋白质组和转录组变化

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Formaldehyde (FA), a ubiquitous volatile organic compound present in a wide range of resources, is a hazardous chemical and human carcinogen. Contamination of FA in food, especially perishable commodities like fish and meat, is a major source of exposure, although it is not recommended for use in food and food products owing to its carcinogenicity. Effects of oral feeding of FA have been studied by evaluating general health, haematology and clinical chemistry in rat. Recent studies have shown that FA exposure leads to detrimental cardiovascular effects. It regulates vascular tensions through nitric oxide-cGMP signalling pathway and ion channels in rats. Although FA is an established carcinogen, molecular studies on carcinogenic potential with dose dependency are meagre. In this context, the present study was undertaken to investigate the toxicogenomic and proteomic alterations in liver of rats fed FA through drinking water. By proteomic analysis, 621 proteins/protein-subunits showed differential abundance (proteome data available via ProteomeXchange with identifier PXD010534), whereas 536 differentially-expressed-genes were identified by transcriptome analysis (data available via Sequence Read Archive with identifier SRR7974113). Gene ontology analysis showed that binding, catalysis, signal transduction were affected in formaldehyde-fed rats. Pathway analysis revealed that formaldehyde-exposure activated PI3K-AKT pathway that leads to inhibition of caspase activity thereby assisting cells to survive against apoptosis. Decreased abundance/down-regulation of ANGPT, eNOS, STAT3 proteins/transcripts and increased abundance of EDN1 indicated decrease in angiogenesis and vasodilatation that restricted hepatic cells from becoming tumorigenic; thus, indicating FA could be less toxic and non-tumorigenic at low concentrations. (C) 2019 Elsevier Ltd. All rights reserved.
机译:甲醛(FA)是一种存在于多种资源中的普遍存在的挥发性有机化合物,是一种有害的化学物质和人类致癌物。食物中的FA尤其是易腐商品如鱼和肉的污染是主要的暴露源,尽管由于其致癌性而不建议在食品和食品中使用。已通过评估大鼠的总体健康,血液学和临床化学研究了口服FA的效果。最近的研究表明,暴露于FA会导致有害的心血管作用。它通过一氧化氮-cGMP信号传导途径和大鼠离子通道调节血管张力。尽管FA是一种公认​​的致癌物,但是有关致癌潜力与剂量依赖性的分子研究还很少。在这种情况下,进行本研究以研究通过饮用水喂养FA的大鼠肝脏中的毒理基因组和蛋白质组学变化。通过蛋白质组学分析,共有621个蛋白质/蛋白质亚基显示出差异丰度(通过蛋白质组数据可通过ProteomeXchange获得,其标识符为PXD010534),而通过转录组分析可鉴定出536个差异表达基因(该数据可通过序列读取存档,标识符为SRR7974113)。基因本体分析表明,甲醛喂养的大鼠的结合,催化,信号转导受到影响。途径分析显示甲醛暴露激活的PI3K-AKT途径导致caspase活性的抑制,从而帮助细胞抵抗凋亡。 ANGPT,eNOS,STAT3蛋白/转录物的丰度/下调减少以及EDN1的丰度增加表明血管生成和血管舒张减少,从而限制了肝细胞的致瘤性。因此,表明FA在低浓度下可能具有较低的毒性和非致瘤性。 (C)2019 Elsevier Ltd.保留所有权利。

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