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Mechanism of arteriosclerosis evoked by production and processing of HB-EGF induced by nitric oxide

Research Project

Project/Area Number 13670151
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionHyogo College of Medicine

Principal Investigator

SUZUKI Keiichiro  Hyogo College of Medicine, Professor, 医学部, 教授 (70221322)

Co-Investigator(Kenkyū-buntansha) EGUCHI Hironobu  Hyogo College of Medicine, Research Associate, 医学部, 助手 (60351798)
YAMAGUCHI Yukihiro  Hyogo College of Medicine, Research Associate, 医学部, 助手 (60330453)
OOKAWARA Tomomi  Hyogo College of Medicine, Assistant Professor, 医学部, 講師 (50330452)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,900,000 (Direct Cost: ¥1,900,000)
KeywordsNitric oxide / HB-EGF / arterioselerosis / reactive oxygen species / smooth muscle cells / JNK / アポトーシス / HP-EGF
Research Abstract

Nitric oxide (NO) serves as an important signal transducer in several cells and tissues, including blood vessels and neuronal and for smooth muscle cells, and its anti-apoptotic effect hematopoietic cells. It is generally thought that NO is involved in the regulation of a wide variety of biological processes, including smooth muscle relaxation, neurotransmission, inhibition of platelet aggregation, immune regulation, and cellular differentiation.
Heparin-binding EGF-like growth factor (HB-EGF), a member of the epidermal growth factor (EGF) family, is produced in smooth muscle cells as well as the macrophages of atherosclerotic plaques and plays an important role in atherogenesis. Recent studies have shown that pro-HB-EGF, a membrane-anchored precursor, may promote the survival of renal epithelial and hepatoma cells.
In this study, we describe the effect of nitric oxide (NO) on the expression of the heparin-binding EGF-like growth factor (HB-EGF), a potent chemoattractant and mitogen for … More smooth muscle cells, and its anti-apoptotic effect against NO cytotoxicity. Previous studies have shown that glutathione peroxidase (GPx), a major peroxide scavenging enzyme is selectively inactivated by an NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), in vitro and in vivo and results in the accumulation of peroxide. The SNAP or peroxynitrite induces HB-EGF through the inactivation of GPx and the accumulation of peroxide. This induction is accompanied by JNK and c-Jun/AP-1 activation. The blocking of the HB-EGF induction by curcumin, c-jun antisense oligonucleotide, and a dominant-negative mutant of JNK1 provides support for these results. A longer pretreatment of rat aortic smooth muscle cells (RASMCs) by SNAP, induces HB-EGF and reduces the TNF-+actinomycin D-induced apoptosis. This protection is blocked by an tisense HB-EGF soligonucleotide. These findings indicate that the induction of HB-EGF by NO would be an adaptive response as an autocrine protective factor againsapoptosis by NO in RASMCs. Less

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Koh YH, et al.: "Inactivation of glutathione peroxidase by NO leads to the accumulation of H_2O_2 and the induction of HB-EGF via c-Jun NH_2-terminal kinase in rat aortic smooth muscle cells"FASEB J.. 15. 1472-1474 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koh YH, et al.: "Osmotic stress induces HB-EGF gene expression via Ca2+/JNK signal cascades in rat aortic smooth muscle cells"J Biochem.. 130. 351-358 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki K, et al.: "Enzyme-linked immunosorbent assay for human and rat Mn-superoxide dismutases"Methods Enzymol.. 349. 129-141 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eguchi H, et al.: "Oxidative Damage Due to Copper Ion and Hydrogen Peroxide Induces GlcNAc-Specific Cleavage of an Asn-Linked Oligosaccharide"J. Biochem.. 131. 477-484 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Park YS, et al.: "Induction of thioredoxin reductase gene expression by peroxynitrite in human umbilical vein endothelial cells"Biol. Chem.. 383. 683-691 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Park YS, et al.: "Identification of the Binding Site of Methylglyoxal on Glutathione Peroxidase : Methylglyox al Inhibits Glutathione Peroxidase Activity via Binding to Glutathione Binding Sites Arg 184 and 185"Free Rad. Res.. 37. 205-211 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koh YH, et al.: "Inactivation of glutathione peroxidase by NO leads to the accumulation of H_2O_2 and the induction of HB-EGF via c-Jun NH_2-terminal kinase in rat aortic smooth muscle cells"FASEB J.. 15. 1472-1474 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Koh YH, et al.: "Osmotic stress induces HB-EGF gene expression via Ca2+/JNK signal cascades in rat aortic smooth muscle cells"J Biochem. 130. 351-358 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Obata H, et al.: "Dye terminator re-cycle-sequencing method : Phage plaque direct sequencing"Analytical Biochem. 272. 102-105 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kizaki T, et al.: "Negative Regulation of LPS-Stimulated Expression of Inducible Nitric Oxide Synthase by AP-1 in Macrophage Cell Line J774A.I."Biochem Biophys Res Commun. 289. 1031-1038 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukui S, et al.: "Post-ischemic transcriptional and translational responces of EC-SOD in mouse brain and serum"Free Rad.Biol.Medicine. 32. 289-298 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki K, et al.: "Enzyme-linked immunosorbent assay for human and rat Mn-superoxide dissimutates"Methods Enzymol. 349. 129-141 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Eguchi H, et al.: "Oxidative Damage Due to Copper Ion and Hydrogen Peroxide Induces GlcNAc-Specific Cleavage of an Asn-Linked Oligosaccharide"J.Biochem. 131. 477-484 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Park YS, et al.: "Induction of thioredoxin reductase gene expression by peroxynitrite in human umbilical vein endothelial cells"Biol.Chem.. 383. 683-691 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yamamoto K, et al.: "Myocardial stiffness is determined by ventricular fibrosis, but not by compensatory or excessive hypertrophy in hypertensive heart"Cardiovasc.Res.. 55. 76-82 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Park YS, et al.: "Identification of the Binding Site of Methylglyoxal on Glutathione Peroxidase : Methylglyoxal Inhibits Glutathione Peroxidase Activity via Binding to Glutathione Binding Sites Arg 184 and 185"Free Rad.Res.. 37. 205-211 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Fukui S. et al.: "Post-ischemic transcriptional and translational responses of EC SOD in mouse brain and serum"Free Rad. Biol. Medicine. 32. 289-298 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kizaki T. et al.: "Stress-and aging-associated modulation of macrophage functions"Environmental Health and Preventive Medicine. 6. 218-228 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki K, et al.: "Enzyme-linked immunosorbent assay for human and rat Mn-superoxide dismutase"Methods Enzymol.. 349. 129-141 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Eguchi H, et al.: "Oxidative Damage Due to Copper Ion and Hydrogen Peroxide Induces GlcNAc-Specific Cleavage of an Asn-Linked Oligosaccharide"J. Biochem.. 131. 477-484 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Park YS, et al.: "Induction of thioredoxin reductase gene expression by peroxynitrite in human umbilical vein endothelial cells"Biol. Chem.. 383. 683-691 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamamoto K. et al.: "Myocardial stiffness is determined by ventricular fibrosis, but not by compensatory or excessive hypertrophy in hypertensive heart"Cardiovasc. Res.. 55. 76-82 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koh YH, et al.: "Inactivation of glutathione peroxidase by NO leads to the accumulation H_2O_2 and the induction of HB-EGF via c-Jun NH_2-terminal kinase in rat aortic smooth muscle cells"FASEB J.. 15. 1472-1474 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koh YH, et al.: "Osmotic stress induces HB-EGF gene expression vis Ca2+/JNK signal cascades in rat aortic smooth muscle cells"J Biochem. 130. 351-358 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Obata H, et al.: "Dye terminator re-cycle-sequencing method : Phage plaque direct sequencing"Analytical Biochem. 272. 102-105 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kizaki T, et al.: "Negative Regulation of LPS-Stimulated Expression of inducible Nitric Oxide Synthase by AP-1 in Macrophage Cell Line J774A.1"Biochem Biophys Res Commun.. 289. 1031-1038 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koh YH, et al.: "Inactivation of glutathione peroxidase by NO leads to the accumulation H_2O_2 and the induction of HB-EGF via c-Jun NH_2-terminal kinase in rat aortic smooth muscle cells"FASEB J.. 15. 1472-1474 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Koh YH, et al.: "Osmotic stress induces HB-EGF gene expression vis Ca2+/JNK signal cascades in rat aortic smooth muscle cells"J Biochem. 130. 351-358 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Obata H, et al.: "Dye terminator re-cycle-sequencing method : Phage plaque direct sequencing"Analytical Biochem. 272. 102-105 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kizaki T, et al.: "Negative Regulation of LPS-Stimulated Expression of inducible Nitric Oxide Synthase by AP-1 in Macrophage Cell Line J774A.1"Biochem Biophys Res Commun.. 289. 1031-1038 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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