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砷暴露斑马鱼(Danio rerio)的蛋白质组学分析以性别特异性方式鉴定出参与纤维化和脂质摄取的蛋白质表达改变。

Proteomic analysis of arsenic-exposed zebrafish (Danio rerio) identifies altered expression in proteins involved in fibrosis and lipid uptake in a gender-specific manner.

机构信息

Graduate School for Biomedical Sciences and Engineering, University of Maine, Orono, ME, USA.

出版信息

Toxicol Sci. 2013 Jul;134(1):83-91. doi: 10.1093/toxsci/kft086. Epub 2013 Apr 9.

DOI:10.1093/toxsci/kft086
PMID:23570992
Abstract

The zebrafish (Danio rerio) was used to investigate protein expression in the liver following arsenic exposure. Several disorders have been linked to arsenic exposure, including cancer, diabetes, and cardiovascular disease. The mechanisms of arsenic toxicity are poorly understood. Prior studies have described altered gene expression, inflammation, and mitogenic signaling in acute or chronic exposure models. A proteomic approach was employed to investigate arsenic-induced alteration in the zebrafish liver proteome following a 7-day exposure to 50 ppb sodium arsenite. Over 740 unique proteins were identified, with fewer than 2% showing differential expression. Molecular pathway analysis software identified lipid metabolism and transport as potential molecular targets. Immunoblots were used to confirm protein expression changes, whereas qPCR was employed to investigate gene expression changes. Overall, 25 proteins were differentially expressed in a gender-specific manner, 11 in males and 14 in females. Of these 25, a single protein, hydroxysteroid dehydrogenase like 2, showed decreased expression in both males and females following arsenic exposure. These findings indicate that protein expression is altered following arsenic exposure. The changes presented here seem to be most prevalent in lipid transport and metabolic pathways, suggesting a potential increase in fibrosis in males and decreased lipid accumulation and uptake in females.

摘要

斑马鱼(Danio rerio)被用于研究砷暴露后肝脏中的蛋白质表达。已有多项研究表明,砷暴露与多种疾病相关,包括癌症、糖尿病和心血管疾病。砷的毒性机制尚未完全阐明。先前的研究已经描述了在急性或慢性暴露模型中,基因表达、炎症和有丝分裂信号的改变。本研究采用蛋白质组学方法,研究了斑马鱼肝脏蛋白质组在 50 ppb 亚砷酸钠暴露 7 天后的变化。鉴定出超过 740 种独特的蛋白质,其中只有不到 2%的蛋白质表达发生差异。分子途径分析软件确定了脂质代谢和运输是潜在的分子靶点。免疫印迹用于验证蛋白质表达变化,而 qPCR 用于研究基因表达变化。总的来说,25 种蛋白质在性别特异性方面表现出差异表达,其中男性 11 种,女性 14 种。在这 25 种蛋白质中,只有一种名为羟甾类脱氢酶类似物 2 的蛋白质在雄性和雌性中均表现出砷暴露后的表达降低。这些发现表明,蛋白质表达在砷暴露后发生改变。这里呈现的变化似乎在脂质转运和代谢途径中最为常见,这表明男性中纤维化的潜在增加和女性中脂质积累和摄取的减少。

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