PMID- 19958400
OWN - NLM
STAT- MEDLINE
DCOM- 20100120
LR  - 20240418
IS  - 1365-2613 (Electronic)
IS  - 0959-9673 (Print)
IS  - 0959-9673 (Linking)
VI  - 90
IP  - 6
DP  - 2009 Dec
TI  - Relationship of impairment induced by intracellular S-adenosylhomocysteine 
      accumulation with DNA methylation in human umbilical vein endothelial cells 
      treated with 3-deazaadenosine.
PG  - 638-48
LID - 10.1111/j.1365-2613.2009.00687.x [doi]
AB  - The aim of this study was to estimate the relationship of endothelial dysfunction 
      induced by intracellular S-adenosylhomocysteine (SAH) accumulation and DNA 
      methylation in human umbilical vein endothelial cells (HUVEC). The isolated HUVEC 
      were incubated with 3-deazaadenosine (DZA) to induce experimental intracellular 
      SAH accumulation. The impairment of HUVEC function was assessed by changes in 
      morphology and proliferative ability. The expression of DNA methyltransferase-1 
      (DNMT1) and the atherosclerosis related genes [oestrogen receptor-alpha 
      (ER-alpha), extracellular superoxide dismutase (EC-SOD) and monocyte 
      chemoattractant protein-1 (MCP-1)] were analysed using quantitative real-time 
      PCR. Global DNA methylated status was measured using the cytosine extension 
      assay. The methylated patterns of ER-alpha, EC-SOD and MCP-1 genes were 
      determined with methylation-specific PCR. We found that DZA administration 
      increased intracellular SAH levels progressively and simultaneously decreased Hcy 
      content in medium. Moreover, the supplementation induced HUVEC apoptosis, 
      inhibited proliferation ability and DNMT1 mRNA expression (P < 0.05) and 
      furthermore reduced global DNA methylation status (P < 0.05). Correlation 
      analysis showed the presence of a negative correlation between intracellular SAH 
      concentration, proliferative ability, and expression of ER-alpha, EC-SOD, and 
      DNMT1 (r = -0.89, -0.86, -0.92 and -0.88 respectively, P < 0.001); and a positive 
      correlation with MCP-1 expression and DNA [(3)H]-dCTP incorporation (r = 0.89 and 
      0.93 respectively, P < 0.001). Our results showed that endothelial dysfunction 
      induced by intracellular SAH accumulation is mediated by regulating the 
      expression of atherosclerosis related genes in HUVEC, which is not related with 
      gene promoter methylated patterns, but may be associated with altered global DNA 
      hypomethylated status. These findings suggest that SAH can act as the potential 
      molecular biological marker in the promotion of atherogenesis.
FAU - Yu, Xiaoping
AU  - Yu X
AD  - Department of Public Health, School of Preclinical Medicine, Chengdu Medical 
      College, Chengdu, Sichuan, China.
FAU - Ling, Wenhua
AU  - Ling W
FAU - Mi, Mantian
AU  - Mi M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int J Exp Pathol
JT  - International journal of experimental pathology
JID - 9014042
RN  - 0 (Chemokine CCL2)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (RNA, Messenger)
RN  - 037V4520IY (3-deazaadenosine)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 979-92-0 (S-Adenosylhomocysteine)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 1.15.1.1 (SOD3 protein, human)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferase 1)
RN  - EC 2.1.1.37 (DNA (Cytosine-5-)-Methyltransferases)
RN  - EC 2.1.1.37 (DNMT1 protein, human)
RN  - M351LCX45Y (Tubercidin)
SB  - IM
MH  - Apoptosis
MH  - Atherosclerosis/genetics
MH  - Cell Proliferation
MH  - Chemokine CCL2/metabolism
MH  - DNA (Cytosine-5-)-Methyltransferase 1
MH  - DNA (Cytosine-5-)-Methyltransferases/genetics
MH  - *DNA Methylation
MH  - Endothelial Cells/cytology/drug effects/*metabolism/physiology
MH  - Estrogen Receptor alpha/metabolism
MH  - Gene Expression
MH  - Homocysteine/metabolism
MH  - Humans
MH  - Infant, Newborn
MH  - Intracellular Membranes/*metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Microscopy, Electron
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/metabolism
MH  - S-Adenosylhomocysteine/*metabolism
MH  - Superoxide Dismutase
MH  - Tubercidin/*pharmacology
MH  - Umbilical Veins/cytology/*metabolism
PMC - PMC2803255
EDAT- 2009/12/05 06:00
MHDA- 2010/01/21 06:00
PMCR- 2010/12/01
CRDT- 2009/12/05 06:00
PHST- 2009/12/05 06:00 [entrez]
PHST- 2009/12/05 06:00 [pubmed]
PHST- 2010/01/21 06:00 [medline]
PHST- 2010/12/01 00:00 [pmc-release]
AID - IEP687 [pii]
AID - 10.1111/j.1365-2613.2009.00687.x [doi]
PST - ppublish
SO  - Int J Exp Pathol. 2009 Dec;90(6):638-48. doi: 10.1111/j.1365-2613.2009.00687.x.