PMID- 11104691
OWN - NLM
STAT- MEDLINE
DCOM- 20010201
LR  - 20181113
IS  - 0264-6021 (Print)
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 352 Pt 3
IP  - Pt 3
DP  - 2000 Dec 15
TI  - Homocysteine stimulates nuclear factor kappaB activity and monocyte 
      chemoattractant protein-1 expression in vascular smooth-muscle cells: a possible 
      role for protein kinase C.
PG  - 817-26
AB  - Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that stimulates 
      the migration of monocytes into the intima of arterial walls. Although many 
      factors that induce MCP-1 expression have been identified, the effect of 
      homocysteine on the expression of MCP-1 in atherogenesis and the underlying 
      mechanisms are not entirely clear. The objective of the present study was to 
      investigate the role of homocysteine in MCP-1 expression in human aorta vascular 
      smooth-muscle cells (VSMCs). After VSMCs were incubated with homocysteine for 
      various time periods, a nuclease protection assay and ELISA were performed. 
      Homocysteine (0.05-0.2 mM) significantly increased the expression of MCP-1 mRNA 
      (up to 2. 7-fold) and protein (up to 3.3-fold) in these cells. The increase in 
      MCP-1 expression was associated with the activation of protein kinase C (PKC) as 
      well as nuclear factor kappaB (NF-kappaB). Further investigation demonstrated 
      that the activation of NF-kappaB was the result of a PKC-mediated reduction in 
      the expression of inhibitory protein (IkappaBalpha) mRNA and protein in 
      homocysteine-treated cells. Oxidative stress might also be involved in the 
      activation of NF-kappaB by homocysteine in VSMCs. In conclusion, the present 
      study has clearly demonstrated that the activation of PKC as well as superoxide 
      production followed by activation of NF-kappaB is responsible for 
      homocysteine-induced MCP-1 expression in VSMCs. These results suggest that 
      homocysteine-stimulated MCP-1 expression via NF-kappaB activation may play an 
      important role in atherogenesis.
FAU - Wang, G
AU  - Wang G
AD  - Department of Pharmacology, Institute of Cardiovascular Science and Medicine, 
      Faculty of Medicine, University of Hong Kong, 1/F, Li Shu Fan Building, 5 Sassoon 
      Road, Pokfulam, Hong Kong, People's Republic of China.
FAU - Siow, Y L
AU  - Siow YL
FAU - O, K
AU  - O K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Phosphoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 9007-49-2 (DNA)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Blotting, Western
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis/genetics/metabolism
MH  - DNA/genetics/metabolism
MH  - DNA-Binding Proteins/biosynthesis/genetics/metabolism
MH  - Enzyme Activation/drug effects
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - *I-kappa B Proteins
MH  - Models, Biological
MH  - Muscle, Smooth, Vascular/cytology/*drug effects/enzymology/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/antagonists & inhibitors/*metabolism
MH  - Nuclease Protection Assays
MH  - Oxidative Stress/drug effects
MH  - Phosphoproteins/biosynthesis/genetics/metabolism
MH  - Protein Binding/drug effects
MH  - Protein Kinase C/antagonists & inhibitors/*metabolism
MH  - RNA, Messenger/analysis/genetics
MH  - Superoxide Dismutase/antagonists & inhibitors/metabolism
MH  - Up-Regulation/drug effects
PMC - PMC1221522
EDAT- 2000/12/06 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/06/15
CRDT- 2000/12/06 11:00
PHST- 2000/12/06 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/06 11:00 [entrez]
PHST- 2001/06/15 00:00 [pmc-release]
PST - ppublish
SO  - Biochem J. 2000 Dec 15;352 Pt 3(Pt 3):817-26.