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大鼠睾丸中3-氯-1,2-丙二醇及3-氯-1,2-丙二醇二棕榈酸酯毒性的蛋白质组学分析

Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate toxicity in rat testis.

作者信息

Sawada Stefanie, Oberemm Axel, Buhrke Thorsten, Meckert Christine, Rozycki Christel, Braeuning Albert, Lampen Alfonso

机构信息

Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.

Federal Institute for Risk Assessment, Department Food Safety, Max-Dohrn-Str. 8-10, 10589 Berlin, Germany.

出版信息

Food Chem Toxicol. 2015 Sep;83:84-92. doi: 10.1016/j.fct.2015.06.002. Epub 2015 Jun 11.

DOI:10.1016/j.fct.2015.06.002
PMID:26072098
Abstract

Thermal treatment of foodstuff containing fats and salt promotes the formation of 3-chloropropane-1,2-diol (3-MCPD) and its fatty acid esters. 3-MCPD-exposed rats develop testicular lesions and Leydig cell tumors. 3-MCPD and 3-MCPD ester toxicity is thought to be caused by 3-MCPD and its metabolites, since 3-MCPD esters are hydrolyzed in the gut. Inhibition of glycolysis is one of the few known molecular mechanisms of 3-MCPD toxicity. To obtain deeper insight into this process, a comparative proteomic approach was chosen, based on a 28-days repeated-dose feeding study with male Wistar rats. Animals received equimolar doses of 3-MCPD or 3-MCPD dipalmitate. A lower dose of 3-MCPD dipalmitate was also administered. Absence of histopathological changes supported an analysis of early cellular disturbance. Testes were analyzed by two-dimensional gel electrophoresis followed by mass-spectrometric protein identification. Data provide a comprehensive overview of proteomic changes induced by 3-MCPD and 3-MCPD dipalmitate in rat testis in an early phase of organ impairment. Results are compatible with known 3-MCPD effects on reproductive function, substantially extend our knowledge about cellular responses to 3-MCPD and support the hypothesis that toxicity of 3-MCPD and 3-MCPD esters is mediated via common effectors. DJ-1 was identified as a candidate marker for 3-MCPD exposure.

摘要

对含有脂肪和盐分的食品进行热处理会促进3-氯-1,2-丙二醇(3-MCPD)及其脂肪酸酯的形成。接触3-MCPD的大鼠会出现睾丸损伤和睾丸间质细胞瘤。3-MCPD及其酯类的毒性被认为是由3-MCPD及其代谢产物引起的,因为3-MCPD酯类在肠道中会水解。抑制糖酵解是3-MCPD毒性为数不多的已知分子机制之一。为了更深入地了解这一过程,基于对雄性Wistar大鼠进行的为期28天的重复剂量喂养研究,选择了一种比较蛋白质组学方法。动物接受等摩尔剂量的3-MCPD或3-MCPD二棕榈酸酯。还给予了较低剂量的3-MCPD二棕榈酸酯。组织病理学变化的缺失支持了对早期细胞紊乱的分析。通过二维凝胶电泳分析睾丸,随后进行质谱蛋白质鉴定。数据全面概述了在器官损伤早期3-MCPD和3-MCPD二棕榈酸酯在大鼠睾丸中诱导的蛋白质组变化。结果与已知的3-MCPD对生殖功能的影响相符,极大地扩展了我们对细胞对3-MCPD反应的认识,并支持了3-MCPD及其酯类毒性是通过共同效应器介导的这一假说。DJ-1被鉴定为3-MCPD暴露的候选标志物。

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