Relative quantification of the proteomic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model

Relative quantification of the proteomic changes associated with the mycotoxin zearalenone in the H295R steroidogenesis model
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DOI:
10.1016/j.toxicon.2011.08.015
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发表时间:
2011-11-01
期刊:
影响因子:
2.8
通讯作者:
Sorlie, Morten
Sorlie, Morten
中科院分区:
医学4区
文献类型:
--
作者:
Busk, Oyvind L.;Ndossi, Doreen;Sorlie, Morten

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玉米赤霉烯酮(ZEN)是一种具有内分泌干扰作用的真菌毒素,在例如养猪业中具有巨大的经济影响。在结构上,ZEN类似于17 β-雌二醇,因此能够与靶细胞中的雌激素受体(ER)结合。正因为如此,它也被归类为非甾体雌激素,植物雌激素,真菌雌激素和生长促进剂。定量蛋白质组学分析进行了使用稳定同位素标记的氨基酸在细胞培养物(SILAC)后,暴露的类固醇生成细胞模型H295 R与ZEN阐明其对蛋白质调控的影响。ZEN显著调节21种蛋白质,包括具有已知内分泌干扰作用的蛋白质和几种癌基因。此外,使用免疫途径分析的网络分析表明,ZEN影响氧化磷酸化途径和线粒体功能障碍途径,这两种途径先前都被报道参与内分泌功能障碍。(C)2011爱思唯尔有限公司保留所有权利。
Zearalenone (ZEN) is a mycotoxin with endocrine disrupting effects having vast economic implications in e.g. pig farming. Structurally, ZEN resembles 17 beta-estradiol, and thus is able to bind to estrogen receptors (ER) in target cells. Because of this, it is also classified as a non-steroidal estrogen, a phytoestrogen, a mycoestrogen, and a growth promoter. Quantitative proteomic analysis was undertaken using stable-isotope labeling by amino acids in cell culture (SILAC) upon exposure of the steroidogenesis cell model H295R with ZEN to elucidate its effect on protein regulation. ZEN significantly regulated 21 proteins, including proteins with known endocrine disrupting effects and several oncogenes. In addition, network analysis using Ingenuity Pathway Analysis showed that ZEN affected the oxidative phosphorylation pathway and the mitochondrial dysfunction pathway, both previously reported to be involved in endocrine dysfunction. (C) 2011 Elsevier Ltd. All rights reserved.