title: Expression Profiles of SIRT1 and APP Genes in Human Neuroblastoma SK-N-SH Cells Treated with Two Epigenetic Agents.
abstract: In our previous studies, significant hypermethylation of the sirtuin 1 (SIRT1) gene and demethylation of the β-amyloid precursor protein (APP) gene were found in patients with Alzheimer's disease (AD) compared with the normal population. Moreover, the expression of SIRT1 was significantly decreased while that of APP was increased in AD patients. These results indicated a correlation of DNA methylation with gene expression levels in AD patients. To further investigate the epigenetic mechanism of gene modulation in AD, we used two epigenetic drugs, the DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC) and the histone deacetylase inhibitor trichostatin A (TSA), to treat human neuroblastoma SK-N-SH cells in the presence of amyloid β-peptide Aβ25-35(Aβ25-35). We found that DAC and TSA had different effects on the expression trends of SIRT1 and APP in the cell model of amyloid toxicity. Although other genes, such as microtubule-associated protein τ, presenilin 1, presenilin 2, and apolipoprotein E, were up-regulated after Aβ25-35 treatment, no significant differences were found after DAC and/or TSA treatment. These results support the evidence in AD patients and reveal a strong correlation of SIRT1/APP expression with DNA methylation and/or histone modification, which may help understand the pathogenesis of AD.
authors: Medical Genetic Centre, Guangdong Women and Children Hospital, Guangzhou, 510010, China.|Maternal and Children Metabolic-Genetic Key Laboratory, Guangdong Women and Children Hospital, Guangzhou, 510010, China.
authors: Yaping
authors: Y
authors: Hou
authors: School of Food Science and Engineering, South China University of Technology, Guangzhou, 510640, China.
authors: Fanghua
authors: F
authors: Wang
authors: Dongsheng Hospital of Guangzhou, 375 People's Road, Guangzhou, 510120, China.
authors: Linping
authors: L
authors: Cheng
authors: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, 510080, China.
authors: Tao
authors: T
authors: Luo
authors: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, 510080, China.
authors: Jie
authors: J
authors: Xu
authors: Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat-sen University, 74 Zhongshan Second Road, Guangzhou, 510080, China. wanghq@mail.sysu.edu.cn.
authors: Huaqiao
authors: H
authors: Wang
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival; D000077209:Decitabine; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D009447:Neuroblastoma / Q000473:pathology; D010446:Peptide Fragments / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D006877:Hydroxamic Acids; D010446:Peptide Fragments; D012333:RNA, Messenger; C074636:amyloid beta-protein (25-35); C012589:trichostatin A; D000077209:Decitabine; D056564:Sirtuin 1; D001374:Azacitidine
keywords: Alzheimer’s disease; DNA methylation; Histone modification; Sirtuin 1; Trichostatin A