PMID- 12145301
OWN - NLM
STAT- MEDLINE
DCOM- 20021113
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 39
DP  - 2002 Sep 27
TI  - Insulin activates CCAAT/enhancer binding proteins and proinflammatory gene 
      expression through the phosphatidylinositol 3-kinase pathway in vascular smooth 
      muscle cells.
PG  - 36631-9
AB  - Phosphatidylinositol 3-kinase (PI3K) is a key molecule mediating signals of 
      insulin in vascular smooth muscle cells (VSMCs). To examine the effect of chronic 
      activation of PI3K on the gene expression of VSMCs, membrane-targeted p110CAAX, a 
      catalytic subunit of PI3K, was overexpressed in rat VSMCs by adenovirus-mediated 
      gene transfer. Similar to insulin's effects, cells overexpressing p110CAAX 
      exhibited a 10- to 15-fold increase in monocyte chemoattractant protein-1 (MCP-1) 
      mRNA expression as compared with the control cells. Electrophoretic mobility 
      shift assay analysis showed that the overexpression of p110CAAX activated neither 
      the NF-kappaB binding nor the activator protein (AP-1) binding activities. We 
      found that two CCAAT/enhancer binding protein (C/EBP) binding sites located 
      between 2.6 and 3.6 kb upstream of the MCP-1 gene were responsible for the 
      induction by p110CAAX. The overexpression of C/EBP-beta and C/EBP-delta but not 
      C/EBP-alpha caused 6- to 8-fold induction of MCP-1 promoter activity. 
      Consistently, the overexpression of p110CAAX as well as insulin induced mRNA 
      expression and nuclear expression of C/EBP-beta and C/EBP-delta in VSMCs. These 
      results clearly indicate that the activation of PI3K induced proinflammatory gene 
      expression through activating C/EBP-beta and C/EBP-delta but not NF-kappaB, which 
      may explain the proinflammatory effect of insulin in the insulin-resistant state.
FAU - Sekine, Osamu
AU  - Sekine O
AD  - Division of Endocrinology and Metabolism, Department of Medicine, Shiga 
      University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
FAU - Nishio, Yoshihiko
AU  - Nishio Y
FAU - Egawa, Katsuya
AU  - Egawa K
FAU - Nakamura, Takaaki
AU  - Nakamura T
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 - 20020726
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (Cebpd protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Insulin)
RN  - 0 (RNA, Messenger)
RN  - 0 (Transcription Factors)
RN  - 142662-43-9 (CCAAT-Enhancer-Binding Protein-delta)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Blotting, Western
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - CCAAT-Enhancer-Binding Protein-delta
MH  - CCAAT-Enhancer-Binding Proteins/*metabolism
MH  - Catalytic Domain
MH  - Cell Line
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Endothelium, Vascular/*cytology
MH  - Enzyme Inhibitors/pharmacology
MH  - *Gene Expression Regulation
MH  - Insulin/*metabolism
MH  - Insulin Resistance
MH  - Male
MH  - Models, Genetic
MH  - Muscle, Smooth/*cytology
MH  - Mutagenesis, Site-Directed
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Plasmids/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Binding
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Swine
MH  - *Transcription Factors
EDAT- 2002/07/30 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/07/30 10:00
PHST- 2002/07/30 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/07/30 10:00 [entrez]
AID - S0021-9258(18)36641-9 [pii]
AID - 10.1074/jbc.M206266200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Sep 27;277(39):36631-9. doi: 10.1074/jbc.M206266200. Epub 2002 
      Jul 26.