Linked Life Data

17805460

Source:http://linkedlifedata.com/resource/pubmed/id/17805460

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2007-9-6
pubmed:abstractText
Hyperhomocysteinemia (HHcy), which is an independent risk factor for atherosclerosis, might cause dysregulation of gene expression, but the characteristics and key links involved in its pathogenic mechanisms are still poorly understood. The objective of the present study was to investigate the effect of HHcy on DNA methylation and the underlying mechanism of homocysteine (Hcy)-induced DNA methylation. HHcy was induced in Sprague-Dawley rats after 4 weeks of a low, medium or high methionine diet. The levels of total homocysteine, S-adenosylmethionine (AdoMet) and S-adenosylhomocysteine (AdoHcy) were detected by high-performance liquid chromatography. The expression levels of genes and proteins of S-adenosylhomocysteine hydrolase, DNA methyltransferase and methyl-CpG-binding domain 2 were detected by real-time reverse transcription-polymerase chain reaction and Western blot analysis. A high-throughput quantitative methylation assay using fluorescence-based real-time polymerase chain reaction was employed to determine the levels of DNA methylation. The results indicated that HHcy induced the elevation of AdoHcy concentration, the decline of AdoMet concentration, the ratios of AdoMet/AdoHcy and the RNA and protein expression of S-adenosylhomocysteine hydrolase and methyl-CpG-binding domain 2, as well as an increase of DNA methyltransferase activity. With different methylation-dependent restriction endonucleases, the aberrant demethylation was found to prefer CCGG sequences to CpG islands. Increasing levels of HHcy significantly increased genome hypomethylation in B1 repetitive elements. The impacts of different levels of HHcy showed that the varied detrimental effects of HHcy could be attributed to different concentrations through different mechanisms. In mild and moderate HHcy, the Hcy might primarily influence the epigenetic regulation of gene expression through the interference of transferring methyl-group metabolism. However, at high Hcy concentrations, the impacts might be more injurious through oxidative stress, apoptosis and inflammation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1672-9145
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
657-67
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Hyperhomocysteinemia-mediated DNA hypomethylation and its potential epigenetic role in rats.
pubmed:affiliation
Department of Pathophysiology, Ningxia Medical College, Yinchuan 750004, China. jwcjyd@163.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't