PMID- 25189662
OWN - NLM
STAT- MEDLINE
DCOM- 20150617
LR  - 20140922
IS  - 1791-244X (Electronic)
IS  - 1107-3756 (Linking)
VI  - 34
IP  - 5
DP  - 2014 Nov
TI  - Homocysteine reduces protein S-nitrosylation in endothelium.
PG  - 1277-85
LID - 10.3892/ijmm.2014.1920 [doi]
AB  - Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease. The 
      S-nitrosylation of proteins is involved in the regulation of cardiovascular 
      functions. However, whether homocysteine (Hcy) impairs vascular functions through 
      the inhibition of protein S-nitrosylation in the endothelium remains to be 
      determined. The experiments were performed in human umbilical vein endothelial 
      cells (HUVECs). Male Sprague‑Dawley rats, with or without administration of 
      L-methionine, were used for the in vivo validation of findings. S-nitrosylation 
      was analyzed using immunofluorescence for nitrosocysteine, and further confirmed 
      by the biotin switch method. The levels of reactive oxygen species (ROS) were 
      detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA) staining. The levels of 
      nitric oxide (NuOmicron) were determined by the nitrate reduction method. Protein 
      expression was analysed by western blot analysis. The activity of nuclear factor 
      kappaB (NF-kappaB) was evaluated by an electrophoretic mobility shift assay (EMSA). The 
      levels of plasma Hcy were measured by ELISA. The results showed that Hcy 
      significantly reduced the levels of protein S-nitrosylation in HUVECs and 
      endothelial S-nitrosylation of aorta. This reduction of protein S-nitrosylation 
      was accompanied by increasing ROS, decreasing phosphorylation levels of Akt and 
      endothelial nitric oxide synthase (eNOS), and reduced levels of nitric oxide in 
      HUVECs. In addition, it was found that Hcy increased the protein expression of 
      vascular cell adhesion molecule-1 by attenuating the cytoplasm S-nitrosylation of 
      NF-kappaB (p65). These data suggested that Hcy impairs endothelial functions by 
      inhibiting endothelial protein S-nitrosylation.
FAU - Chen, Yulong
AU  - Chen Y
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong 
      University Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
FAU - Zhao, Sihai
AU  - Zhao S
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
FAU - Wang, Yanli
AU  - Wang Y
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
FAU - Li, Yafeng
AU  - Li Y
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
FAU - Bai, Liang
AU  - Bai L
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
FAU - Liu, Ruihan
AU  - Liu R
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
FAU - Fan, Jianglin
AU  - Fan J
AD  - Department of Molecular Pathology, Interdisciplinary Graduate School of Medicine 
      and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan.
FAU - Liu, Enqi
AU  - Liu E
AD  - Research Institute of Atherosclerotic Disease, Xi'an Jiaotong University 
      Cardiovascular Research Center, Xi'an, Shaanxi 710061, P.R. China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140904
PL  - Greece
TA  - Int J Mol Med
JT  - International journal of molecular medicine
JID - 9810955
RN  - 0 (Protein S)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.14.13.39 (NOS3 protein, human)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 1.14.13.39 (Nos3 protein, rat)
RN  - Homocysteinemia
SB  - IM
MH  - Animals
MH  - Aorta/drug effects/metabolism
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Homocysteine/*pharmacology
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Hyperhomocysteinemia/drug therapy
MH  - Male
MH  - Methionine/administration & dosage
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type III/genetics/metabolism
MH  - Phosphorylation
MH  - Protein S/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/metabolism
MH  - Transcription Factor RelA/genetics/metabolism
MH  - Vascular Cell Adhesion Molecule-1/genetics/metabolism
EDAT- 2014/09/06 06:00
MHDA- 2015/06/18 06:00
CRDT- 2014/09/06 06:00
PHST- 2014/02/09 00:00 [received]
PHST- 2014/08/13 00:00 [accepted]
PHST- 2014/09/06 06:00 [entrez]
PHST- 2014/09/06 06:00 [pubmed]
PHST- 2015/06/18 06:00 [medline]
AID - 10.3892/ijmm.2014.1920 [doi]
PST - ppublish
SO  - Int J Mol Med. 2014 Nov;34(5):1277-85. doi: 10.3892/ijmm.2014.1920. Epub 2014 Sep 
      4.