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暴露于雌激素内分泌干扰物乙炔雌二醇后,海洋雄性鱼类花鲈肝脏蛋白质组发生广泛改变。

Widespread alterations upon exposure to the estrogenic endocrine disruptor ethinyl estradiol in the liver proteome of the marine male fish Cyprinodon variegatus.

机构信息

Centro de Investigación Mariña da Universidade de Vigo (CIM-UVigo), Vigo, Galicia, Spain; Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.

Centro de Investigación Mariña da Universidade de Vigo (CIM-UVigo), Vigo, Galicia, Spain; Department of Ecology and Animal Biology, University of Vigo, Vigo, Galicia, Spain.

出版信息

Aquat Toxicol. 2022 Jul;248:106189. doi: 10.1016/j.aquatox.2022.106189. Epub 2022 May 4.

DOI:10.1016/j.aquatox.2022.106189
PMID:35537357
Abstract

Quantitative proteomic changes in the liver of adult males of Sheepshead minnow (Cyprinodon variegatus) upon exposure to ethinyl estradiol (EE2) were assessed to provide an advanced understanding of the metabolic pathways affected by estrogenic endocrine disruption in marine fish, and to identify potential novel molecular biomarkers for the environmental exposure to estrogens. From a total of 3188 identified protein groups (hereafter proteins), 463 showed a statistically significant difference in their abundance between EE2 treatment and solvent control samples. The most affected biological processes upon EE2 exposure were related to ribosomal biogenesis, protein synthesis and transport of nascent proteins to endoplasmic reticulum, and nuclear mRNA catabolism. Within the group of upregulated proteins, a subset of 14 proteins, involved in egg production (Vitellogenin, Zona Pellucida), peptidase activity (Cathepsine E, peptidase S1, Serine/threonine-protein kinase PRP4 homolog, Isoaspartyl peptidase and Whey acidic protein), and nucleic acid binding (Poly [ADP-ribose] polymerase 14) were significantly upregulated with fold-change values higher than 3. In contrast, Collagen alpha-2, involved in the process of response to steroid hormones, among others, was significantly downregulated (fold change = 0.2). This pattern of alterations in the liver proteome of adult males of C. variegatus can be used to identify promising novel biomarkers for the characterization of exposure of marine fish to estrogens. The Whey acidic protein-like showed the highest upregulation in EE2-exposed individuals (21-fold over controls), suggesting the utility of abundance levels of this protein in male liver as a novel biomarker of xenoestrogen exposure.

摘要

定量蛋白质组学变化在成年雄性羊头鱼(Cyprinodon variegatus)的肝脏暴露于雌二醇(EE2)以提供先进的了解受雌激素内分泌干扰的代谢途径在海洋鱼类,并确定潜在的新的分子生物标志物的环境暴露于雌激素。从总共 3188 个鉴定的蛋白质组中,有 463 个在 EE2 处理和溶剂对照样品之间的丰度上存在统计学上的显著差异。在 EE2 暴露后受影响最严重的生物学过程与核糖体生物发生、蛋白质合成和新生蛋白质向内质网的运输以及核 mRNA 分解代谢有关。在上调蛋白组中,有一组 14 种蛋白,参与卵母细胞生成(卵黄蛋白原、透明带蛋白)、肽酶活性(组织蛋白酶 E、肽酶 S1、丝氨酸/苏氨酸蛋白激酶 PRP4 同源物、异天冬氨酸肽酶和乳清酸性蛋白)和核酸结合(多聚[ADP-核糖]聚合酶 14)显著上调,倍数变化值高于 3。相比之下,胶原 alpha-2,参与类固醇激素反应等过程,显著下调(倍数变化=0.2)。C. variegatus 成年雄性肝脏蛋白质组的这种改变模式可用于鉴定有前途的新型生物标志物,用于表征海洋鱼类暴露于雌激素。乳清酸性蛋白样在 EE2 暴露个体中表现出最高的上调(对照的 21 倍),表明该蛋白在雄性肝脏中的丰度水平可作为一种新型的外源性雌激素暴露生物标志物。

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