PMID- 15829559
OWN - NLM
STAT- MEDLINE
DCOM- 20050923
LR  - 20200930
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 289
IP  - 3
DP  - 2005 Sep
TI  - Bidirectional regulation of monocyte chemoattractant protein-1 gene at distinct 
      sites of its promoter by nitric oxide in vascular smooth muscle cells.
PG  - C582-90
AB  - We have previously reported that chronic activation of phosphatidylinositol 
      3-kinase (PI3-kinase) by the overexpression of membrane-targeted p110CAAX induced 
      proinflammatory gene expression in rat vascular smooth muscle cells (VSMCs) 
      through the induction of CCAAT/enhancer binding protein-beta (C/EBP-beta) and 
      C/EBP-delta. To examine the anti-inflammatory effect of nitric oxide (NO) on 
      proinflammatory gene expression, we have investigated the effects of sodium 
      nitroprusside (SNP) on the monocyte chemoattractant protein-1 (MCP-1) gene 
      expression in VSMCs under chronic activation of PI3-kinase. At low concentrations 
      (0.05 mM) of SNP, but not at high concentrations (0.5-1.0 mM), MCP-1 mRNA and 
      protein expression as well as its transcriptional activity were significantly 
      reduced. We found that SNP induced C/EBP homologous protein (CHOP) expression, 
      which inhibited C/EBP binding activity and reduced the C/EBP activity induced by 
      chronic activation of PI3-kinase in a dose-dependent manner up to 1.0 mM. 
      Consistently, the increase in CHOP expression significantly reduced the MCP-1 
      promoter activity induced by PI3-kinase. However, the overexpression of CHOP 
      alone upregulated MCP-1 promoter activity in a dose-dependent manner up to high 
      concentrations. Deletion analysis of MCP-1 promoter and electrophoretic mobility 
      shift assay identified the CHOP-response element (CHOP-RE) at the region between 
      -190 and -179 bp of MCP-1 promoter. By using CHOP-RE as a decoy, we significantly 
      suppressed the increase in promoter activity of MCP-1 induced by either CHOP or 
      SNP. Thus CHOP induced by an NO donor has bidirectional effects on MCP-1 gene 
      expression: it decreases gene expression by inhibition of C/EBPs, and it 
      increases the gene expression through CHOP-RE.
FAU - Kodama, Ken-ichi
AU  - Kodama K
AD  - Division of Endocrinology and Metabolism, Dept. of Medicine, Shiga University of 
      Medical Science, Otsu, Shiga 520-2192, Japan.
FAU - Nishio, Yoshihiko
AU  - Nishio Y
FAU - Sekine, Osamu
AU  - Sekine O
FAU - Sato, Yoshinori
AU  - Sato Y
FAU - Egawa, Katsuya
AU  - Egawa K
FAU - Maegawa, Hiroshi
AU  - Maegawa H
FAU - Kashiwagi, Atsunori
AU  - Kashiwagi A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050413
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Ddit3 protein, rat)
RN  - 0 (Nitric Oxide Donors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 147336-12-7 (Transcription Factor CHOP)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - CCAAT-Enhancer-Binding Proteins/genetics/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics
MH  - Gene Expression/drug effects/physiology
MH  - Male
MH  - Muscle, Smooth, Vascular/cytology/*physiology
MH  - Nitric Oxide/*metabolism
MH  - Nitric Oxide Donors/pharmacology
MH  - Nitroprusside/pharmacology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Promoter Regions, Genetic/*physiology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Response Elements/physiology
MH  - Transcription Factor CHOP
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic/drug effects/physiology
EDAT- 2005/04/15 09:00
MHDA- 2005/09/24 09:00
CRDT- 2005/04/15 09:00
PHST- 2005/04/15 09:00 [pubmed]
PHST- 2005/09/24 09:00 [medline]
PHST- 2005/04/15 09:00 [entrez]
AID - 00558.2004 [pii]
AID - 10.1152/ajpcell.00558.2004 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2005 Sep;289(3):C582-90. doi: 
      10.1152/ajpcell.00558.2004. Epub 2005 Apr 13.