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城市污染驱动的蛋白质组变化表明,颗粒物可能会扰乱大鼠大脑的能量代谢、线粒体活性和氧化途径。

Proteomic changes driven by urban pollution suggest particulate matter as a deregulator of energy metabolism, mitochondrial activity, and oxidative pathways in the rat brain.

机构信息

BIOSCOPE Group, LAQV-REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal; Proteomass Scientific Society, Rua dos Inventores, Madan Park, 2829-516, Caparica, Portugal.

Department of Neurosurgery, Cedars-Sinai Medical Center, 127 S. San Vicente Blvd, Los Angeles, CA 90048, United States.

出版信息

Sci Total Environ. 2019 Oct 15;687:839-848. doi: 10.1016/j.scitotenv.2019.06.102. Epub 2019 Jun 10.

Abstract

The adverse effects of air pollution have been long studied in the lung and respiratory systems, but the molecular changes that this causes at the central nervous system level have yet to be fully investigated and understood. To explore the evolution with time of protein expression levels in the brain of rats exposed to particulate matter of different sizes, we carried out two-dimensional gel electrophoresis followed by determination of dysregulated proteins through Coomassie blue staining-based densities (SameSpots software) and subsequent protein identification using MALDI-based mass spectrometry. Expression differences in dysregulated proteins were found to be statistically significant with p-value <0.05. A systems biology-based approach was utilized to determine critical biochemical pathways involved in the rats' brain response. Our results suggest that rats' brains have a particulate matter size dependent-response, being the mitochondrial activity and the astrocyte function severely affected. Our proteomic study confirms the dysregulation of different biochemical pathways involving energy metabolism, mitochondrial activity, and oxidative pathways as some of the main effects of PM exposure on the rat brain. SIGNIFICANCE: Rat brains exposed to particulate matter with origin in car engines are affected in two main areas: mitochondrial activity, by the dysregulation of many pathways linked to the respiratory chain, and neuronal and astrocytic function, which stimulates brain changes triggering tumorigenesis and neurodegeneration.

摘要

空气污染对肺部和呼吸系统的不良影响早已得到广泛研究,但这种影响在中枢神经系统水平上引起的分子变化尚未得到充分研究和理解。为了探究暴露于不同大小颗粒物的大鼠大脑中蛋白质表达水平随时间的变化,我们进行了二维凝胶电泳,然后通过考马斯亮蓝染色密度(SameSpots 软件)确定失调蛋白,并使用 MALDI 质谱进行后续蛋白鉴定。通过统计学分析发现,失调蛋白的表达差异具有统计学意义(p 值<0.05)。我们还利用基于系统生物学的方法来确定大鼠大脑反应中涉及的关键生化途径。研究结果表明,大鼠大脑对颗粒物大小具有依赖性反应,其中线粒体活性和星形胶质细胞功能受到严重影响。我们的蛋白质组学研究证实,不同生化途径的失调涉及能量代谢、线粒体活性和氧化途径,这是 PM 暴露对大鼠大脑的主要影响之一。研究意义:本研究证实了源于汽车发动机的颗粒物对大鼠大脑的影响主要集中在两个方面:线粒体活性,通过与呼吸链相关的许多途径的失调来调节;神经元和星形胶质细胞功能,这会刺激大脑发生变化,从而引发肿瘤形成和神经退行性变。

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