title: Lead exposure in pheochromocytoma cells induces persistent changes in amyloid precursor protein gene methylation patterns.
abstract: 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.
authors: 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.
authors: Yuan-Yuan
authors: YY
authors: Li
authors: Tian
authors: T
authors: Chen
authors: Yanjian
authors: Y
authors: Wan
authors: Shun-qing
authors: SQ
authors: Xu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007854:Lead / Q000633:toxicity*; D009942:Organometallic Compounds / Q000633:toxicity; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D051381:Rats
chemical_list: D016564:Amyloid beta-Protein Precursor; D009942:Organometallic Compounds; D007854:Lead; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619382:Dnmt1 protein, rat; C008261:lead acetate