https://scholars.lib.ntu.edu.tw/handle/123456789/406755
標題: | The epigenetic effects of amyloid-£]1-40 on global DNA and neprilysin genes in murine cerebral endothelial cells | 作者: | Chen K.-L. Wang S.S.-S. Yang Y.-Y. Yuan R.-Y. Chen R.-M. Hu C.-J. |
關鍵字: | Alzheimer's disease;Amyloid-£];Cerebral amyloid angiopathy;DNA methylation;Neprilysin | 公開日期: | 2009 | 卷: | 378 | 期: | 1 | 起(迄)頁: | 57-61 | 來源出版物: | Biochemical and Biophysical Research Communications | 摘要: | Amyloid-£] (A£]) is the core component of senile plaques, which are the pathological markers for Alzheimer's disease and cerebral amyloid angiopathy. DNA methylation/demethylation plays a crucial role in gene regulation and could also be responsible for presentation of senescence. Oxidative stress, which may be induced by A£], is thought to be an important contributor of DNA hyper-methylation; however, contradicting this is the fact that global DNA hypo-methylation has been found in aging brains. It therefore remains largely unknown as to whether A£] does in fact cause DNA methylation/demethylation. Neprilysin (NEP) is one of the enzymes responsible for A£] degradation, with its expression decreasing in both Alzheimer and aging brains. Using high-performance liquid chromatography (HPLC), we explore whether A£] is responsible for alteration of the global DNA methylation status on a murine cerebral endothelial cells model, and also use methylation-specific PCR (MSPCR) to examine whether DNA methylation status is altered on the NEP promoter region. We find that A£] reduces global DNA methylation whilst increasing NEP DNA methylation and further suppressing the NEP expression in mRNA and protein levels. Our results support that A£] induces epigenetic effects, implying that DNA methylation may be part of a vicious cycle involving the reduction in NEP expression along with a resultant increase in A£] accumulation, and that A£] may induce global DNA hypo-methylation. ? 2008 Elsevier Inc. All rights reserved. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/406755 | ISSN: | 0006291X | DOI: | 10.1016/j.bbrc.2008.10.173 |
顯示於: | 化學工程學系 |
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