PMID- 11216856
OWN - NLM
STAT- MEDLINE
DCOM- 20010521
LR  - 20190818
IS  - 0300-8177 (Print)
IS  - 0300-8177 (Linking)
VI  - 216
IP  - 1-2
DP  - 2001 Jan
TI  - Homocysteine stimulates the expression of monocyte chemoattractant protein-1 in 
      endothelial cells leading to enhanced monocyte chemotaxis.
PG  - 121-8
AB  - Hyperhomocysteinemia has been identified as an independent risk factor for 
      atherosclerosis. The infiltration of monocytes into the arterial wall is one of 
      the key events during atherogenesis. Monocyte chemoattractant protein-1 (MCP-1) 
      is a potent chemokine that stimulates the migration of monocytes into the intima 
      of the arterial wall. The mechanism by which increased monocyte infiltration 
      occurs in atherosclerotic lesions in patients with hyperhomocysteinemia has not 
      been delineated. The objective of the present study was to investigate the effect 
      of homocysteine on MCP-1 production in endothelial cells. Cells were incubated 
      with homocysteine. The secretion of MCP-1 protein was significantly increased 
      (195% as compared to the control) in cells treated with pathological 
      concentrations of homocysteine. Such effect was accompanied by an increased 
      expression of MCP-1 mRNA (176% as compared to the control) in endothelial cells 
      which resulted in enhanced monocyte chemotaxis. The p38 MAP kinase as well as 
      other members of the p38 MAP kinase pathway, including MKK3, MKK6, ATF-2 and 
      Elk-1, were activated in homocysteine-treated cells. Homocysteine-induced MCP-1 
      expression and subsequent monocyte chemotaxis were blocked by a p38 MAP kinase 
      inhibitor (SB203580) suggesting that the p38 MAP kinase pathway might be involved 
      in homocysteine-induced MCP-1 expression in endothelial cells. In contrast, 
      staurosporine, a protein kinase C inhibitor, had no effect on 
      homocysteine-induced MCP-1 expression. In conclusion, our results indicate that 
      homocysteine stimulates MCP-1 expression in endothelial cells leading to enhanced 
      monocyte chemotaxis.
FAU - Sung, F L
AU  - Sung FL
AD  - Department of Pharmacology, Institute of Cardiovascular Science and Medicine, 
      Faculty of Medicine, University of Hong Kong, Hong Kong.
FAU - Slow, Y L
AU  - Slow YL
FAU - Wang, G
AU  - Wang G
FAU - Lynn, E G
AU  - Lynn EG
FAU - O, K
AU  - O K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Mol Cell Biochem
JT  - Molecular and cellular biochemistry
JID - 0364456
RN  - 0 (ATF2 protein, human)
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (ELK1 protein, human)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Imidazoles)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Pyridines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 3)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 6)
RN  - EC 2.7.12.2 (MAP2K3 protein, human)
RN  - EC 2.7.12.2 (MAP2K6 protein, human)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - H88EPA0A3N (Staurosporine)
RN  - OU13V1EYWQ (SB 203580)
SB  - IM
MH  - Activating Transcription Factor 2
MH  - Blotting, Western
MH  - Calcium-Calmodulin-Dependent Protein Kinases/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*biosynthesis
MH  - *Chemotaxis
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - *DNA-Binding Proteins
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*metabolism
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Homocysteine/metabolism/*physiology
MH  - Humans
MH  - Imidazoles/pharmacology
MH  - MAP Kinase Kinase 3
MH  - MAP Kinase Kinase 6
MH  - Mitogen-Activated Protein Kinase Kinases/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/*metabolism
MH  - Protein Kinase C/antagonists & inhibitors
MH  - Protein-Tyrosine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Pyridines/pharmacology
MH  - RNA, Messenger/metabolism
MH  - Staurosporine/pharmacology
MH  - Time Factors
MH  - Transcription Factors/metabolism
MH  - Umbilical Veins/metabolism
MH  - ets-Domain Protein Elk-1
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2001/02/24 12:00
MHDA- 2001/05/25 10:01
CRDT- 2001/02/24 12:00
PHST- 2001/02/24 12:00 [pubmed]
PHST- 2001/05/25 10:01 [medline]
PHST- 2001/02/24 12:00 [entrez]
AID - 10.1023/a:1017383916068 [doi]
PST - ppublish
SO  - Mol Cell Biochem. 2001 Jan;216(1-2):121-8. doi: 10.1023/a:1017383916068.