Insight into the effect of a heavy metal mixture on neurological damage in rats through combined serum metabolomic and brain proteomic analyses.
Insight into the effect of a heavy metal mixture on neurological damage in rats through combined serum metabolomic and brain proteomic analyses.
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DOI：
10.1016/j.scitotenv.2023.165009
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发表时间：
2023-06
期刊：
影响因子：
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通讯作者：
Jie Xie;Fankun Zhou;L. Ouyang;Qi Li;Shaoqi Rao;Rui Su;Shuo Yang;Jiajun Li;Xin Wan
中科院分区：
文献类型：
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作者：
Jie Xie;Fankun Zhou;L. Ouyang;Qi Li;Shaoqi Rao;Rui Su;Shuo Yang;Jiajun Li;Xin Wan
引起神经认知障碍的重金属铅（Pb）、镉（Cd）和汞（Hg）已被广泛研究。这些元素通常不会单独存在于环境中;它们通常与其他重金属一起发现，可以通过各种途径进入人体，从而影响健康。我们以前的研究表明，低水平的铅，镉，汞导致断奶和成年大鼠的神经行为障碍。然而，很少有人知道的生物标志物和机制的铅，镉，汞混合物引起的神经功能障碍。代谢组学和蛋白质组学数据的综合分析可能揭示重金属诱导的代谢和蛋白质谱的改变，从而提高我们对重金属诱导的神经损伤的分子机制的理解。因此，脑组织和血清样品收集暴露于铅，镉，汞混合物的蛋白质组学和代谢组学分析，分别从大鼠。分析显示，363差异蛋白质在大脑和206代谢物在血清中唯一改变的铅，镉，汞混合物暴露组，与对照组相比。影响代谢的主要途径是不饱和脂肪酸的生物合成、亚油酸代谢、苯丙氨酸代谢和色氨酸代谢。我们进一步确定，花生四烯酸（C20：4 n-3）和肾上腺酸（C22：4 n-3）的水平升高，犬尿烯酸（KA）和喹啉酸（QA）的水平和KA/QA的比例，在组中暴露于铅，镉，汞混合物。蛋白质组和代谢组的联合分析表明，显著改变的蛋白质，如LPCAT 3，SLC 7A 11，ASCL 4和KYAT 1可能参与重金属混合物诱导的神经损伤。总的来说，我们假设铁下垂和犬尿氨酸途径的失调与长期暴露于重金属混合物引起的神经损伤有关。
The heavy metals lead (Pb), cadmium (Cd), and mercury (Hg) that cause neurocognitive impairment have been extensively studied. These elements typically do not exist alone in the environment; they are often found with other heavy metals and can enter the body through various routes, thereby impacting health. Our previous research showed that low Pb, Cd, and Hg levels cause neurobehavioral impairments in weaning and adult rats. However, little is known about the biomarkers and mechanisms underlying Pb, Cd, and Hg mixture-induced neurological impairments. A combined analysis of metabolomic and proteomic data may reveal heavy metal-induced alterations in metabolic and protein profiles, thereby improving our understanding of the molecular mechanisms underlying heavy metal-induced neurological impairments. Therefore, brain tissue and serum samples were collected from rats exposed to a Pb, Cd, and Hg mixture for proteomic and metabolomic analyses, respectively. The analysis revealed 363 differential proteins in the brain and 206 metabolites in serum uniquely altered in the Pb, Cd, and Hg mixture exposure group, compared to those of the control group. The main metabolic impacted pathways were unsaturated fatty acids biosynthesis, linoleic acid metabolism, phenylalanine metabolism, and tryptophan metabolism. We further identified that the levels of arachidonic acid (C20:4 n-3) and, adrenic acid (C22:4 n-3) were elevated and that kynurenic acid (KA) and quinolinic acid (QA) levels and the KA/QA ratio, were decreased in the group exposed to the Pb, Cd, and Hg mixture. A joint analysis of the proteome and metabolome showed that significantly altered proteins such as LPCAT3, SLC7A11, ASCL4, and KYAT1 may participate in the neurological impairments induced by the heavy metal mixture. Overall, we hypothesize that the dysregulation of ferroptosis and kynurenine pathways is associated with neurological damage due to chronic exposure to a heavy metal mixture.