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双酚 A 暴露大鼠大脑皮质蛋白质组的改变:一项蛋白质组学研究。

Alteration of protein profile in cerebral cortex of rats exposed to bisphenol a: a proteomics study.

机构信息

Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.

Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Neurotoxicology. 2020 May;78:1-10. doi: 10.1016/j.neuro.2020.01.013. Epub 2020 Feb 1.

Abstract

Bisphenol A (BPA) is one of the most widely used chemicals in plastic industry, which enters the human body through occupational and food contact. We studied the protein changes in rat cerebral cortex to evaluate the neurotoxicity of BPA. Twenty-four adult male rats were randomly selected and divided into four groups and each group respectively received 0, 0.5, 5 and 50 mg/kg of BPA for 4 weeks orally. To determine the oxidative status, reduced glutathione content and the level of malondialdehyde were measured in brain cortical tissue. The proteins of each sample extracted and separated on a two-dimensional acrylamide gel electrophoresis. From the obtained protein map, the 10 most altered protein spots were used for mass spectroscopy analysis. The lipid peroxidation in both doses of 0.5 and 5 mg/kg was significantly higher than the control group, but the glutathione content had no significant difference between the groups. Based on the results of the MS data analysis by the MASCOT database search engine, 10 proteins with altered intensity were identified as pyruvate kinase, alpha-enolase, aconitate hydratase, creatine kinase B-type, phosphatidylethanolamine-binding protein 1, 14-3-3 protein eta, guanine nucleotide-binding protein subunit beta-1, dihydropyrimidinase-related protein 2, glutamine synthetase and the neurofilament light polypeptide. There are several reports suggesting that the increase or decrease in the level and activity of these 10 proteins, similar to those observed in this study, is related to some neurological and psychosocial disorders including neurodegenerative diseases, schizophrenia, depression, epilepsy and some brain tumors.

摘要

双酚 A(BPA)是塑料工业中使用最广泛的化学物质之一,它通过职业和食物接触进入人体。我们研究了大鼠大脑皮质中的蛋白质变化,以评估 BPA 的神经毒性。随机选择 24 只成年雄性大鼠,并将它们分为四组,分别经口给予 0、0.5、5 和 50mg/kg 的 BPA 4 周。为了确定氧化状态,测量了大脑皮质组织中的还原型谷胱甘肽含量和丙二醛水平。从每个样本中提取蛋白质并在二维丙烯酰胺凝胶电泳上分离。从获得的蛋白质图谱中,使用质谱分析了 10 个变化最明显的蛋白质斑点。两种剂量(0.5 和 5mg/kg)的脂质过氧化明显高于对照组,但各组之间的谷胱甘肽含量没有显著差异。基于通过 MASCOT 数据库搜索引擎对 MS 数据分析的结果,鉴定出 10 种强度改变的蛋白质,分别为丙酮酸激酶、α-烯醇酶、乌头酸水合酶、肌酸激酶 B 型、磷酸乙醇胺结合蛋白 1、14-3-3 蛋白 eta、鸟嘌呤核苷酸结合蛋白亚基β-1、二氢嘧啶酶相关蛋白 2、谷氨酰胺合成酶和神经丝轻链。有几项报道表明,这些 10 种蛋白质的水平和活性的增加或减少,类似于本研究中观察到的情况,与一些神经和心理社会障碍有关,包括神经退行性疾病、精神分裂症、抑郁症、癫痫和一些脑肿瘤。

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