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尿液代谢组学揭示了孕期金属暴露与氨基酸代谢应激之间的新型相互作用。

Urinary metabolomics reveals novel interactions between metal exposure and amino acid metabolic stress during pregnancy.

作者信息

Wang Mu, Xia Wei, Liu Hongbin, Liu Fang, Li Han, Chang Huailong, Sun Jie, Liu Wenyu, Sun Xiaojie, Jiang Yangqian, Liu Hongxiu, Wu Chuansha, Pan Xinyun, Li Yuanyuan, Rang Weiqing, Lu Songfeng, Xu Shunqing

机构信息

Key Laboratory of Environment and Health , Ministry of Education & Ministry of Environmental Protection , and State Key Laboratory of Environmental Health (Incubation) , School of Public Health , Tongji Medical College , Huazhong University of Science and Technology , Wuhan , Hubei , People's Republic of China . Email:

School of Computer Science and Technology , Huazhong University of Science and Technology , Wuhan , Hubei , People's Republic of China . Email:

出版信息

Toxicol Res (Camb). 2018 Jul 24;7(6):1164-1172. doi: 10.1039/c8tx00042e. eCollection 2018 Nov 1.

DOI:10.1039/c8tx00042e
PMID:30510686
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6220731/
Abstract

Pregnant women are a unique group undergoing profound structural modifications in uterus, breast, adipose tissue and extracellular fluids. Amino acid metabolic stress is a unique physical process that occurs during pregnancy. Metals constitute a fundamental part of the maternal body and have a universal effect on amino acid metabolism. However, the exact interaction between metals and amino acid metabolism during pregnancy is unknown. The aim of the present study was to determine the correlations of metals with amino acid metabolic intermediates in the urine of 232 healthy pregnant women in their first, second and third trimesters during normal pregnancy. Sixteen metals in the urine of 232 healthy pregnant women in their first, second and third trimesters were quantified using inductively coupled plasma mass spectrometry (ICP-MS). An ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometer (UPLC-QTOFMS)-based metabolomics approach was conducted to detect intermediate products involved in amino acid metabolism during the entire pregnancy period. A panel regression model was established to investigate the relationship between urine metals and amino acid metabolism. Seven metals-cadmium, cobalt, copper, cesium, manganese, thallium and vanadium-showed significant association with amino acid metabolic intermediates, including 2-oxoarginine, 3-indoleacetonitrile, indole, indole-5,6-quinone, 2-succinyl-l-glutamic acid 5-semialdehyde, -methyltryptamine and -succinyl-l,l-2,6-diaminopimelate, in the healthy pregnant women. These findings indicated that exposure to cadmium, cobalt, copper, cesium, manganese, thallium and vanadium significantly affected the metabolic status of tryptophan, arginine, proline, tyrosine and lysine metabolism in the maternal body during normal pregnancy.

摘要

孕妇是一个独特的群体,其子宫、乳房、脂肪组织和细胞外液正在经历深刻的结构变化。氨基酸代谢应激是孕期发生的一个独特生理过程。金属是母体身体的基本组成部分,对氨基酸代谢具有普遍影响。然而,孕期金属与氨基酸代谢之间的确切相互作用尚不清楚。本研究的目的是确定正常孕期232名处于孕早期、孕中期和孕晚期的健康孕妇尿液中金属与氨基酸代谢中间体的相关性。采用电感耦合等离子体质谱法(ICP-MS)对232名处于孕早期、孕中期和孕晚期的健康孕妇尿液中的16种金属进行定量分析。采用基于超高效液相色谱四极杆飞行时间质谱仪(UPLC-QTOFMS)的代谢组学方法,检测整个孕期氨基酸代谢过程中的中间产物。建立了面板回归模型,以研究尿液中金属与氨基酸代谢之间的关系。七种金属——镉、钴、铜、铯、锰、铊和钒——与健康孕妇的氨基酸代谢中间体显著相关,这些中间体包括2-氧代精氨酸、3-吲哚乙腈、吲哚、吲哚-5,6-醌、2-琥珀酰-L-谷氨酸5-半醛、N-甲基色胺和N-琥珀酰-L,L-2,6-二氨基庚二酸。这些发现表明,在正常孕期,接触镉、钴、铜、铯、锰、铊和钒会显著影响母体中色氨酸、精氨酸、脯氨酸、酪氨酸和赖氨酸代谢的代谢状态。

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