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大鼠暴露于邻苯二甲酸酯后肾上腺类固醇生成的 mRNA 表达和蛋白质-蛋白质相互作用(PPI)网络分析。

mRNA expression and protein-protein interaction (PPI) network analysis of adrenal steroidogenesis in response to exposure to phthalates in rats.

机构信息

Department of Medical Elementology and Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.

Department of Pharmacology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.

出版信息

Environ Toxicol Pharmacol. 2022 Jan;89:103780. doi: 10.1016/j.etap.2021.103780. Epub 2021 Dec 2.

DOI:10.1016/j.etap.2021.103780
PMID:34864161
Abstract

Phthalate esters such as di-butyl phthalate (DBP) and di-ethyl hexyl phthalate (DEHP) used in personal care and consumer products and medical devices have potential to affect human health. We studied the effect of DBP and DEHP on critical enzymes of glucocorticoid biosynthesis pathway in the adrenal gland and pro-inflammatory cytokines in the serum in male Wistar rats. DEHP and DBP treatment altered the mRNA expression of enzymes of glucocorticoid biosynthesis pathway accompanied by a reduction in glucocorticoid production and elevation in the level of glucocorticoid regulated pro-inflammatory cytokines indicating a cascading effect of phthalates. The analysis of PPI (protein - protein interaction) network involving Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) of enzymes through STRING database revealed that all the proteins have the maximum level of interaction with the selected number of proteins. The STRING database analysis together with in vivo data indicates the potential effects of phthalates on various targets of steroidogenesis pathway with a global biological impact.

摘要

邻苯二甲酸酯如邻苯二甲酸二丁酯(DBP)和邻苯二甲酸二(2-乙基己基)酯(DEHP),用于个人护理和消费产品以及医疗器械,有可能影响人类健康。我们研究了 DBP 和 DEHP 对肾上腺糖皮质激素生物合成途径关键酶和血清中促炎细胞因子的影响雄性 Wistar 大鼠。DEHP 和 DBP 处理改变了糖皮质激素生物合成途径的酶的 mRNA 表达,伴随着糖皮质激素产生减少和糖皮质激素调节的促炎细胞因子水平升高,表明邻苯二甲酸酯具有级联效应。通过 STRING 数据库对涉及京都基因与基因组百科全书(KEGG)途径和酶的基因本体论(GO)的 PPI(蛋白质-蛋白质相互作用)网络进行分析表明,所有蛋白质与所选数量的蛋白质具有最高水平的相互作用。STRING 数据库分析与体内数据共同表明,邻苯二甲酸酯对类固醇生成途径的各种靶标具有潜在影响,具有全局生物学影响。

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