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2004 Fiscal Year Final Research Report Summary

Functional analysis of a novel apoptosis-inducing gene upregulated in atherosclerotic lesions

Research Project

Project/Area Number 15603003
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 細胞死(アポトーシス)
Research InstitutionMukogawa Women's University

Principal Investigator

FUKUO Keisuke  Mukogawa Women's University, Food Sciences & Nutrition, Professor, 生活環境学部, 教授 (40156758)

Co-Investigator(Kenkyū-buntansha) YASUDA Osamu  Osaka University medical School, Geriatric Medicine, Assistant Professor, 医学系研究科, 助手 (00372615)
Project Period (FY) 2003 – 2004
KeywordsApoptosis / Mitochondria / Gene / Cytochrome C / Atherosclerosis
Research Abstract

Apoptosis, a programmed cell death, regulates many physiological homeostasis. Its deregulation is known to link to many human diseases such as cancer, neurodegenerative disorders, and atherosclerosis (Science 258:468,1992). There are two major pathways for induction of apoptosis. One is the extrinsic or receptor-mediated pathway represented by Fas and tumor necrosis factor α receptor. The other is the intrinsic pathway, in which mitochondria play a crucial role by releasing cytochrome C from the inter-membrane space into the cytoplasm. In this study, we have identified a novel gene upregulated in atherosclerotic lesions in apolipoprotein E-deficient mice, which are a model of atherosclerosis caused by hyperlipidemia. We compared the gene expression profile of vascular smooth muscle cells(VSMC) cultured from atherosclerotic plaque (P) to that from non-plaque in these mice. We succeeded to clone this novel gene and designated it as Apop-1. In order to clarify the function of this gene, A … More pop-1 expression vector, pcDNA3Apop-1, was introduced into cultured VSMC. Interestingly, introduction of this gene induces apoptosis of VSMC by releasing cytochrome C from mitochondria. The conditioned medium of the transfected cells had no capability to induce apoptosis, indicating that Apop-1-induced apoptosis is not mediated through secretary factors. We also demonstrated that Apop-1 gene has a mitochondria localization signal and Apop-1 protein is actually localized in mitochondria in Apop-1-transfected cells. Bcl-2 family proteins are known to regulate the release of cytochrome C from mitochondria. Importantly unlike Bcl-2 family members, Apop-1 possesses neither Bcl-2 homology (BH) nor carboxy terminal transmembrane (TM) domains. In addition, overexpression of Bcl-2 did not suppress Apop-1-induced apoptosis, suggesting that Apop-1 is a novel pro-apoptotic protein that release cytochrome C from mitochondria. We are now generating Apop-1 knockout mice and an adenoviral gene transfection system to analyze the function of this novel gene. Less

  • Research Products

    (11 results)

All 2004 2003 2002

All Journal Article (11 results)

  • [Journal Article] Homocysteine enhances endothelial apoptosis via upregulation of Fasmediated pathways.2004

    • Author(s)
      Suhara T, Fukuo K, et al.
    • Journal Title

      Hypertension 43

      Pages: 1208-1213

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Fas signaling induces Akt activation and upregulation of endothelial nitric oxide synthase expression.2004

    • Author(s)
      Takemura Y, Fukuo K, et al.
    • Journal Title

      Hypertension 43

      Pages: 880-884

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Homocysteine enhances endothelial apoptosis via upregulation of Fas-mediated pathways.2004

    • Author(s)
      Suhara T, Fukuo K, et al.
    • Journal Title

      Hypertension 43

      Pages: 1208-1213

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Eicosapentaenoic acid protects endothelial cells against anoikis through restoration of cFLIP.2003

    • Author(s)
      Suzuki T, Fukuo K, et al.
    • Journal Title

      Hypertension 42

      Pages: 342-348

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nifedipine upregulates manganese superoxide dismutase expression in vascular smooth muscle cells via endothelial cell-dependent pathways.2003

    • Author(s)
      Fukuo K, et al.
    • Journal Title

      Hypertens.Res. 26

      Pages: 503-508

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Upregulation of cAMP is a new functional signal pathway of Klotho in endothelial cells.2003

    • Author(s)
      Yang J, Matsukawa N, Rakugi H, Imai M, Kida I, Nagai M, Ohta J, Fukuo K.
    • Journal Title

      Biochem Biophys Res Commun. 301

      Pages: 424-429

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nifedipine upregulates manganese superoxide dismutase expression in vascular smooth muscle cells via endothelial cell-dependent pathways.2003

    • Author(s)
      Fukuo K, et al.
    • Journal Title

      Hypertens Res. 26

      Pages: 503-508

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Upregulation of cAMP is a new functional signal pathway of Klotho in endothelial cells.2003

    • Author(s)
      Yang J, Matsukawa N, Rakugi H, Imai M, Kida I, Nagai M, Ohta J, Fukuo K
    • Journal Title

      Biochem Biophys Res Commun. 301

      Pages: 424-429

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Nifedipine indirectly upregulates superoxide dismutase expression in endothelial cells via vascular smooth muscle cell-dependent pathways.2002

    • Author(s)
      Fukuo K, et al.
    • Journal Title

      Circulation 106

      Pages: 356-361

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Nifedipine indirectly upregulates superoxide dismutase expression in endothelial cells via vascular smooth muscle cell-dependent pathways.2002

    • Author(s)
      Fukuo K, et al.
    • Journal Title

      Circulation. 106

      Pages: 356-361

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Increased plasma levels of the soluble form of Fas ligand in patients with acute myocardial infarction and unstable angina pectoris.2002

    • Author(s)
      Shimizu M, Fukuo K, et al.
    • Journal Title

      J Am Coll Cardiol. 39

      Pages: 585-590

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

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Published: 2006-07-11  

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