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甲醛经口喂养大鼠肝脏的蛋白质组学和转录组学变化。

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

机构信息

ICAR-Central Inland Fisheries Research Institute, FREM Division, Biochemistry Laboratory- Proteomics Unit, Barrackpore, Kolkata, 700120, West Bengal, India.

ICAR-Central Inland Fisheries Research Institute, FREM Division, Biochemistry Laboratory- Proteomics Unit, Barrackpore, Kolkata, 700120, West Bengal, India; ICAR-National Rice Research Institute, Crop Protection Division, Cuttack, 753006, India.

出版信息

Chemosphere. 2020 Apr;245:125599. doi: 10.1016/j.chemosphere.2019.125599. Epub 2019 Dec 9.

Abstract

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.

摘要

甲醛(FA)是一种广泛存在的挥发性有机化合物,存在于多种资源中,是一种危险的化学物质和人类致癌物。FA 污染食物,尤其是鱼类和肉类等易腐商品,是暴露的主要来源,尽管由于其致癌性,不建议将其用于食品和食品产品中。通过评估大鼠的一般健康状况、血液学和临床化学,研究了 FA 的口服喂养作用。最近的研究表明,FA 暴露会导致有害的心血管效应。它通过一氧化氮-cGMP 信号通路和大鼠中的离子通道来调节血管张力。尽管 FA 是一种已确立的致癌物,但关于剂量依赖性致癌潜力的分子研究很少。在这种情况下,本研究通过饮用水喂养 FA 来研究大鼠肝脏的毒基因组和蛋白质组变化。通过蛋白质组分析,621 个蛋白质/蛋白质亚基显示出差异丰度(通过 ProteomeXchange 以标识符 PXD010534 提供蛋白质组数据),而通过转录组分析鉴定了 536 个差异表达基因(通过 Sequence Read Archive 以标识符 SRR7974113 提供数据)。GO 分析表明,结合、催化、信号转导在 FA 喂养大鼠中受到影响。通路分析表明,FA 暴露激活了 PI3K-AKT 通路,导致 caspase 活性抑制,从而帮助细胞存活以抵抗细胞凋亡。ANGPT、eNOS、STAT3 蛋白/转录物的丰度降低/下调和 EDN1 的丰度增加表明血管生成和血管舒张减少,从而限制肝细胞发生癌变;因此,表明 FA 在低浓度下可能毒性较小且非致癌。

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