Solaimani Parrisa, Saffari Arian, Sioutas Constantinos, Bondy Stephen C, Campbell Arezoo
Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA, USA.
Department of Civil and Environmental Engineering, University of Southern California, Los Angeles, CA, USA.
Neurotoxicology. 2017 Jan;58:50-57. doi: 10.1016/j.neuro.2016.11.001. Epub 2016 Nov 13.
Exposure to ambient particulate matter (PM) has been associated with the onset of neurodevelopmental and neurodegenerative disorders, but the mechanism of toxicity remains unclear. To gain insight into this neurotoxicity, this study sought to examine global gene expression changes caused by exposure to ambient ultrafine PM. Microarray analysis was performed on primary human neurons derived from fetal brain tissue after a 24h exposure to 20μg/mL of ambient ultrafine particles. We found a majority of the changes in noncoding RNAs, which are involved in epigenetic regulation of gene expression, and thereby could impact the expression of several other protein coding gene targets. Although neurons from biologically different lot numbers were used, we found a significant increase in the expression of metallothionein 1A and 1F in all samples after exposure to particulate matter as confirmed by quantitative PCR. These metallothionein 1 proteins are responsible for neuroprotection after exposure to environmental insult but prolonged induction can be toxic. Epidemiological studies have reported that in utero exposure to ultrafine PM not only leads to neurodevelopmental and behavioral abnormalities, but may also predispose the progeny to neurodegenerative disease later in life by genetic imprinting. Our results pinpoint some of the PM-induced genetic changes that may underlie these findings.
暴露于环境颗粒物（PM）已与神经发育和神经退行性疾病的发病相关，但毒性机制仍不清楚。为深入了解这种神经毒性，本研究旨在检测暴露于环境超细颗粒物所引起的整体基因表达变化。对源自胎儿脑组织的原代人类神经元在暴露于20μg/mL环境超细颗粒24小时后进行微阵列分析。我们发现大多数变化存在于非编码RNA中，这些非编码RNA参与基因表达的表观遗传调控，从而可能影响其他几个蛋白质编码基因靶点的表达。尽管使用了来自生物学上不同批次的神经元，但通过定量PCR证实，我们发现暴露于颗粒物后所有样本中金属硫蛋白1A和1F的表达均显著增加。这些金属硫蛋白1负责在暴露于环境损伤后提供神经保护，但长期诱导可能具有毒性。流行病学研究报告称，子宫内暴露于超细颗粒物不仅会导致神经发育和行为异常，还可能通过基因印记使后代在以后的生活中易患神经退行性疾病。我们的结果指出了一些可能是这些发现基础的PM诱导的基因变化。
