PMID- 18024959
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20210301
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 3
DP  - 2008 Jan 18
TI  - Homocysteine induces monocyte chemoattractant protein-1 expression in hepatocytes 
      mediated via activator protein-1 activation.
PG  - 1282-1292
LID - S0021-9258(20)69620-X [pii]
LID - 10.1074/jbc.M707886200 [doi]
AB  - Hyperhomocysteinemia is characterized by abnormally high concentrations of 
      homocysteine (Hcy) in the plasma. It is a metabolic disorder associated with 
      dysfunction of several organs such as atherosclerosis, altered lipid metabolism, 
      and liver injury. In this study we investigated the effect of Hcy on 
      transcriptional regulation of monocyte chemoattractant protein-1 (MCP-1), a 
      potent chemokine, expression in hepatocytes. Hyperhomocysteinemia was induced in 
      rats by a high-methionine diet for 4 weeks. MCP-1 mRNA and protein levels were 
      significantly elevated in the liver tissue homogenate and in hepatocytes of 
      hyperhomocysteinemic rats. The role of transcription factors in MCP-1 expression 
      was examined by electrophoretic mobility shift assay. Activation of activator 
      protein (AP)-1 but not nuclear factor kappaB was detected in the liver tissue of 
      those rats. Incubation of rat hepatocytes with Hcy (50-200 microm) caused a 
      significant increase in AP-1 activation followed by an increase in intracellular 
      MCP-1 mRNA expression and an elevation of MCP-1 protein secreted into the culture 
      medium. Hcy markedly increased the DNA binding activity of human recombinant AP-1 
      (c-Fos and c-Jun proteins). The presence of a sulfhydryl group in Hcy was 
      essential for Hcy-induced AP-1 activation. When hepatocytes were transfected with 
      decoy AP-1 oligodeoxynucleotide to inhibit AP-1 activation, Hcy-induced MCP-1 
      mRNA expression was abolished. Further analysis revealed that increased hepatic 
      MCP-1 expression was positively correlated with the serum MCP-1 level. These 
      results suggest that Hcy-induced MCP-1 expression in the liver is mediated via 
      AP-1 activation, which may contribute to chronic inflammation associated with 
      hyperhomocysteinemia.
FAU - Woo, Connie W H
AU  - Woo CWH
AD  - Departments of Animal Science and Physiology, University of Manitoba, Canadian 
      Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital 
      Research Centre, Winnipeg R2H 2A6, Canada.
FAU - Siow, Yaw L
AU  - Siow YL
AD  - Departments of Animal Science and Physiology, University of Manitoba, Canadian 
      Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital 
      Research Centre, Winnipeg R2H 2A6, Canada.
FAU - O, Karmin
AU  - O K
AD  - Departments of Animal Science and Physiology, University of Manitoba, Canadian 
      Centre for Agri-Food Research in Health and Medicine, St. Boniface Hospital 
      Research Centre, Winnipeg R2H 2A6, Canada. Electronic address: karmino@sbrc.ca.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071116
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factor RelA)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Chemokine CCL2/blood/*genetics
MH  - DNA/metabolism
MH  - Gene Expression Regulation/*drug effects
MH  - Hepatocytes/*drug effects/*metabolism
MH  - Homocysteine/*pharmacology
MH  - Humans
MH  - Hyperhomocysteinemia
MH  - Kinetics
MH  - Liver/drug effects/metabolism
MH  - Molecular Sequence Data
MH  - NF-kappa B p50 Subunit/metabolism
MH  - Protein Binding/drug effects
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - Proto-Oncogene Proteins c-jun/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Recombinant Proteins/metabolism
MH  - Transcription Factor AP-1/*genetics
MH  - Transcription Factor RelA/metabolism
EDAT- 2007/11/21 09:00
MHDA- 2008/02/15 09:00
CRDT- 2007/11/21 09:00
PHST- 2007/11/21 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2007/11/21 09:00 [entrez]
AID - S0021-9258(20)69620-X [pii]
AID - 10.1074/jbc.M707886200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Jan 18;283(3):1282-1292. doi: 10.1074/jbc.M707886200. Epub 2007 
      Nov 16.