发育性铅暴露与表观遗传调节因子的寿命改变及其与阿尔茨海默病生物标志物的对应关系。
Developmental lead exposure and lifespan alterations in epigenetic regulators and their correspondence to biomarkers of Alzheimer's disease.
作者信息
Eid Aseel, Bihaqi Syed Waseem, Renehan William E, Zawia Nasser H
机构信息
Neurodegeneration Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI, USA; Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, USA; Geroge and Ann Ryan Institute for Neuroscience, University of Rhode Island, Kingston RI, USA.
Department of Pharmacology and Toxicology, University of Hail, Hail, Kingdom of Saudi Arabia.
出版信息
Alzheimers Dement (Amst). 2016 Feb 15;2:123-31. doi: 10.1016/j.dadm.2016.02.002. eCollection 2016.
INTRODUCTION
Early life lead (Pb) exposure results in a latent increase in Alzheimer's disease (AD)-related proteins, and cognitive deficits late in life in both rodents and primates. This study was conducted to investigate if these late life changes were accompanied by epigenetic alterations.
METHODS
Western blot analysis and RT-PCR were used to measure Deoxyribonucleic acid methylation regulators (DNMT1, DNMT3a, MeCP2, MAT2A) and histone proteins (H3K9Ac, H3K4me2, H3K27me3).
RESULTS
Cerebral levels of DNMT1 and MeCP2 were significantly reduced in mice exposed to Pb early in life, whereas the expression of DNMT3a was not altered. Levels of MAT2a were increased in the Pb-exposed mice across the lifespan. H3K9Ac and H3K4me2, involved in gene activation, were decreased, whereas the repressive mark H3K27me3 was elevated.
DISCUSSION
Epigenetic modifiers are affected by the developmental exposure to Pb and may play a role in mediating the latent increases in AD-related proteins in the brain.
引言
早年铅（Pb）暴露会导致啮齿动物和灵长类动物体内与阿尔茨海默病（AD）相关的蛋白质出现潜在增加，并在晚年出现认知缺陷。本研究旨在调查这些晚年变化是否伴随着表观遗传改变。
方法
采用蛋白质免疫印迹分析和逆转录聚合酶链反应（RT-PCR）来检测脱氧核糖核酸甲基化调节因子（DNMT1、DNMT3a、MeCP2、MAT2A）和组蛋白（H3K9Ac、H3K4me2、H3K27me3）。
结果
早年暴露于铅的小鼠大脑中DNMT1和MeCP2的水平显著降低，而DNMT3a的表达未改变。在整个生命周期中，暴露于铅的小鼠体内MAT2a的水平升高。参与基因激活的H3K9Ac和H3K4me2减少，而抑制性标记H3K27me3升高。
讨论
表观遗传修饰因子受发育过程中铅暴露的影响，可能在介导大脑中与AD相关蛋白质的潜在增加中发挥作用。
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