PMID- 17805460
OWN - NLM
STAT- MEDLINE
DCOM- 20071217
LR  - 20190513
IS  - 1672-9145 (Print)
IS  - 1672-9145 (Linking)
VI  - 39
IP  - 9
DP  - 2007 Sep
TI  - Hyperhomocysteinemia-mediated DNA hypomethylation and its potential epigenetic 
      role in rats.
PG  - 657-67
AB  - 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.
FAU - Jiang, Yideng
AU  - Jiang Y
AD  - Department of Pathophysiology, Ningxia Medical College, Yinchuan 750004, China. 
      jwcjyd@163.com
FAU - Sun, Tao
AU  - Sun T
FAU - Xiong, Jiantuan
AU  - Xiong J
FAU - Cao, Jun
AU  - Cao J
FAU - Li, Guizhong
AU  - Li G
FAU - Wang, Shuren
AU  - Wang S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0LVT1QZ0BA (Homocysteine)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/genetics/metabolism
MH  - Base Sequence
MH  - *DNA Methylation
MH  - Disease Models, Animal
MH  - Epigenesis, Genetic/*physiology
MH  - Homocysteine/blood
MH  - Hyperhomocysteinemia/blood/*genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Molecular Sequence Data
MH  - Rabbits
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2007/09/07 09:00
MHDA- 2007/12/18 09:00
CRDT- 2007/09/07 09:00
PHST- 2007/09/07 09:00 [pubmed]
PHST- 2007/12/18 09:00 [medline]
PHST- 2007/09/07 09:00 [entrez]
AID - 10.1111/j.1745-7270.2007.00327.x [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2007 Sep;39(9):657-67. doi: 
      10.1111/j.1745-7270.2007.00327.x.