• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

1997 Fiscal Year Final Research Report Summary

Functional analysis of nitric oxide synthase related genes transfered into cardiomyocytes in viv

Research Project

Project/Area Number 08670761
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

SHIN Wea.Soo  Univ.of Tokyo, Health Service, instructer, 保健管理センター, 助手 (10211971)

Co-Investigator(Kenkyū-buntansha) SAKAMOTO Aiji  Cellular Physiology Laboratory, RIKEN,The Special Postductoral Researcher of RIK, 理科学研究所, 基礎科学研究員 (40291067)
TOYOOKA Teruhiko  University of Tokyo, Faculty of Medicine (Hospital), Professor, 医学部, 教授 (00146151)
Project Period (FY) 1996 – 1997
Keywordsnitric oxide synthase / gene transfered / virus vector / cardiomyocytes / apoptosis / beta-galactosidase / NOS inhibitors / mitochondrial
Research Abstract

Methods
Endothelial nitric oxide synthase(ecNOS)gene has been tranafered into in vivo rat cardiomyocytes with combination of HVJ(Hemagglutinating virus of Japan)and liposomes to examine the direct of nitric oxide in a living heart.
Results
1)The expression of the marker gene, beta-gal(beta-galactosidase)gene was detected 3 days after the gene transfer, reached the maximal level, and still remained 14 days after the in vivo transfer. The efficiency of the gene transfer without HVJ-loposome was less than 10%. The beta-gal gene transfer with HVJ-loposome method did not induce inflammatory findings, and the extent of the gene localized within a intercalated disc which enabled us to distinguish the cellular change by gene transfer from untransfected parts of the same cell.
ecNOS gene transfer into a living geart induced severe tissue damage, unexpectedly. The cardiac tissue damage co-localized with beta-gal and ecNOS transfected area. The gene transfer of less amount(5mug vs.50mug)evoked milder tissue injury. Pretreatment of ^<L->NAME,a NOS inhibitor, suppressed the tissue damage by ecNOS transfection. The area of tissue damage contained accumulation of macrophages and fibrosis with a few area of TUNEL-positive cells. Electronmicroscope showed enlarged and deformed mitochondrial accumulation beside disarray of sarcomeres.
Discussions
ecNOS gene transfer into a living heart which was expected to protect heart from tissue injury induced severe cardiac damage. Influence of the introduced NOS amount or of surrounding condition has been analyzed.

  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Shin, WS.: "Toxic action of nitric oxide on myocardial cell:Direct evidence from ge-ne transfer in vivo." J Cardiac Failure. 2. S149-153 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin, WS.: "The role of nitric oxide in the cardiovascular system." Ann NY Acad Sci. 786. 233-244 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Shin, WS.: "Nitric oxide attenuates vascular smooth muscle cell activation by interf-eron-γ." J Biol Chem. 271. 11317-11324 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang, Y.: "Contribution of sustained Ca^<2+> elevation for nitric oxide producti-on in endothelial cells and subsequent modulation of Ca^<2+> transient in v-ascular smooth muscle cells in coculture." J Biol Chem. 271. 5647-5655 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawaguchi, H.: "In vivo gene transfection of hum-an endothelial cell nitric oxide syntha-se in cardiomyocytes causes apotosis-li-ke cell death:Identification using Send-ai Virus-coated liposomes." Circulation. 95. 2441-2447 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hikiji, H.: "Direct action of nitric oxide on osteoblastic differentiation." FEBS Lett. 410. 238-242 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwasawa, K.: "Effect of extracellular pH on re-ceptor-mediated Ca2+-influx in A7r5 smo-oth muscle:Involvement of two different types of channels." J Physiol. 503. 237-251 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 申 偉秀: "HVJ-liposome法によるカルシウム活性化中性蛋白分解酵素(CANP)関連遺伝子のin vivo導入による心筋変化の解析" 第4回分子循環器研究会講演記録集. 4. 22-24 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 申 偉秀: "HVJ-liposome法による一酸化窒素合成酵素(nitric oxide synthase)関連遺伝子のin vivo導入による心筋変化の解析" 第12回持田記念財団研究成果報告集. 12. 85-88 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Toyo-oka, T.: "Calcium-activated neutral protea-ses and myocardial protein catabolism.In:New Horizon for Failing Heart Syndrome.Sasayama S,ed." Springer-Verlag, 7 (1996)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川口 博之: "NOによる心筋細胞毒性"心不全"(篠山重威 編)" 医薬ジャーナル社, 9 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Wang Y: "Contribution of sustained Ca^<2+> elevation for nitric oxide production in endothelial cells and subsequent modulation of Ca^<2+> transient in vascular smooth muscle cells in coculture." The Journal of Biological Chemistry. 271. 5647-5655 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin WS: "Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma." The Journal of Biological Chemistry. 271. 11317-11324 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin WS: "The role of nitric oxide in the cardiovascular system." The Annals of the New York Academy of Sciences. 786. 33-244 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shin WS.: "Toxic action of nitric oxide on myocardial cell : Direct evidence from gene transfer in vivo." Journal of Cardiac Failure. 2. S149-153 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawaguchi H: "In vivo gene transfection of human endothelial cell nitric oxide synthase in cardiomyocytes causes apotosis-like cell death : Identification using Sendai Virus-coated liposomes." Circulation. 95. 2441-2447 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hikiji H: "Direct action of nitric oxide on osteoblastic differentiation." FEBS Letters. 410. 238-242 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwasawa K: "Effect of extracellular pH on receptormediated Ca2+-influx in A7r5 smooth muscle : Involvement of two different types of channels." Journal of Physioly. 503. 237-251 (1997)

    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 1999-03-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi