2005 Fiscal Year Final Research Report Summary
Identification of the inhibitory factor for the transcription of inflammatory genes in vascular smooth muscle cells
| Project/Area Number |
16590877
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
NISHIO Yoshihiko Shiga University of Medical Science, Department of Medicine, assistant professor, 医学部, 講師 (40281084)
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| Project Period (FY) |
2004 – 2005
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| Keywords | NO / CHOP / MCP-1 / C / EBP / Insulin |
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| Research Abstract |
We have reported that chronic activation of phosphatidylinositol 3-kinase (PI3K) by the overexpression of membrane-targeted p110CAAX induces proinflammatory gene expression in rat vascular smooth muscle cells (VSMCs) through the induction of CCAAT/enhancer binding protein-β (C/EBP-β) and C/EBP-δ. To examine the antiinflammatory effect of nitric oxide (NO) on the proinflammatory gene expression, we investigated the effects of sodium nitroprusside (SNP) on the monocyte chemoattractant protein-1 (MCP-1) gene expression in VSMCs under chronic activation of PI3K. At low concentration (0.05 mM) of SNP, but not at high concentration (0.5-1.0 mM), it significantly reduced MCP-1 mRNA and protein expression as well as its transcriptional activity. 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 PI3K 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 PI3K. However, the overexpression of CHOP alone up-regulated MCP-1 promoter activity in a dose-dependent manner up to high concentration. 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 CHOP-RE used as a decoy, the increase in promoter activity of MCP-1 induced by either CHOP or SNP was suppressed significantly. Thus, CHOP induced by an NO-donor has bidirectional effects on MCP-1 gene expression : it decreases the gene expression by inhibition of C/EBPs, and it increases the gene expression through the CHOP-RE.
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Research Products
(6 results)
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[Journal Article] The Transcription Factor AP-2{beta}Causes Cell Enlargement and insulin Resistance in 3T3-L1 Adipocytes.2006
Author(s)
Tao Y, Maegawa H, Ugi S, Ikeda K, Nagai Y, Egawa K, Nakamura T, Tsukada S, Nishio Y, Maeda S, Kashiwagi A
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Journal Title
Endocrinology 147
Pages: 1685-96
Description
「研究成果報告書概要(和文)」より
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[Journal Article] The Transcription Factor AP-2 {beta} Causes Cell Enlargement and Insulin Resistance in 3T3-L1 Adipocytes.2006
Author(s)
Tao Y, Maegawa H, Ugi S, Ikeda K, Nagai Y, Egawa K, Nakamura T, Tsukada S, Nishio Y, Maeda S, Kashiwagi A
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Journal Title
Endocrinology 147
Pages: 1685-1696
Description
「研究成果報告書概要(欧文)」より
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