The Effect of β-amyloid protein on DNA Methylation in Endothelial Cells
Date Issued
2007
Date
2007
Author(s)
Chen, Wei-Chieh
DOI
zh-TW
Abstract
The abnormality of DNA methylation has been found to be highly associated with many diseases including Alzheimer’s disease. β-amyloid peptide in Alzheimer’s disease plays a pivotal role in the pathogenesis of the disease. Researches showed that β-amyloid peptide self-assembles into stable fibrils with a characteristic cross β-pleated sheet secondary structure during the development of Alzheimer’s disease. Moreover, extensive protein fibrillogenesis or aggregation often occurs resulting in an accumulation of the abnormally folded proteins that damages cells.
Results from previous studies suggested that there exists a certain link between Alzheimer’s disease and DNA methylation. A lower level of total DNA methylation but a higher concentration of homocysteine was found in the patients with Alzheimer’s disease. In addition, the demthylation of presenilin-1 would induce a rapid production in β-amyloid peptides. While a correlation between the aberration of DNA methylation and Alzheimer’s disease pathology has been widely recognized, the detailed interaction mechanism remains rather elusive.
In the study presented here, we propose a hypothesis that β-amyloid peptide in an aggregation state would impact the DNA methylation. In order to test this hypothesis, the murine cerebral endothelial cells (MCEC) were first incubated with various concentrations of aggregated β-amyloid species for 48 hours and the extraction and enzymatic digestion of DNA from these cells were then performed. Via high performance liquid chromatography, the level of total DNA methylation was evaluated by the analysis of the concentrations of 2’-deoxycytidine and 5-methyl-2’-deoxycytidine. Our experimental results indicated that β-amyloid fibrils led to a reduction in the level of total DNA methylation in a concentration dependent manner. A possible explanation for the reduction in the level of DNA methylation is due to the β-amyloid-induced decline in the cell membrane fluidity which leads to a drop in the activity of methylatransferase, and therefore, a decrease in the level of total DNA methylation. However, further investigation is warranted to examine the underlying mechanism(s) of the interaction between
Subjects
DNA甲基化,內皮細胞,貝塔類澱粉蛋白質
DNA mehtylation,Endothelial Cells,β-amyloid protein
Type
thesis
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