Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Environ Toxicol. 2012 Aug;27(8):495-502. doi: 10.1002/tox.20666. Epub 2010 Nov 29.
It has been suggested that lead (Pb) exposure in early life may increase amyloid precursor protein (APP) expression and promote the pathogenesis of Alzheimer's disease in old age. The current study examined whether the DNA methylation patterns of APP gene in rat pheochromocytoma (PC12) cells changed after Pb acetate exposure. Undifferentiated PC12 cells were exposed to three doses of Pb acetate (50, 250, and 500 nM) and one control for 2 days or 1 week. The methylation patterns of APP promoter and global DNA methylation were analyzed. The DNA methyltransferase 1 (DNMT1) expression and the level of amyloid β peptide (Aβ) were also investigated. The results showed that the exposure of the three concentrations of Pb acetate could make the APP promoter hypomethylated. The global DNA methylation level and the expression of DNMT1 were changed in the 500 nM group after 2 days exposure and in the 250 and 500 nM group after 7 days exposure. Thus, Pb may exert neurotoxic effects through mechanisms that alter the global and promoter methylation patterns of APP gene. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.
有人提出，生命早期的铅（Pb）暴露可能会增加淀粉样前体蛋白（APP）的表达，并促进老年阿尔茨海默病的发病机制。本研究探讨了醋酸铅暴露后大鼠嗜铬细胞瘤（PC12）细胞中 APP 基因的 DNA 甲基化模式是否发生改变。未分化的 PC12 细胞分别暴露于三种剂量的醋酸铅（50、250 和 500 nM）和一种对照物 2 天或 1 周。分析 APP 启动子和全基因组 DNA 甲基化模式。还研究了 DNA 甲基转移酶 1（DNMT1）的表达和淀粉样β肽（Aβ）的水平。结果表明，三种浓度的醋酸铅暴露均可使 APP 启动子去甲基化。500 nM 组暴露 2 天后，全基因组 DNA 甲基化水平和 DNMT1 表达发生变化，250 和 500 nM 组暴露 7 天后也发生变化。因此，铅可能通过改变 APP 基因的全基因组和启动子甲基化模式发挥神经毒性作用。©2010 年威利父子公司，环境毒理学，2012 年。
