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Studies for the induction of apoptosis in human junctional and gingival epithelial cells and for protective effect of HGF against apoptosis of these cells

Research Project

Project/Area Number 09671901
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional basic dentistry
Research InstitutionThe University of Tokushima (1998)
Kagoshima University (1997)

Principal Investigator

ARAKAKI Naokatu  The University of Tokushima Faculty of Pharmaceutical Sciences, Associate Professor, 薬学部, 助教授 (60151148)

Co-Investigator(Kenkyū-buntansha) MATSUYAMA Takashi  Kagoshima University, 歯学部, 助手 (40253900)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordshuman junctional epithelial cells / human gingival epithelial cells / apoptosis / hepatocyte growth factor / interleukin-1beta converting enzyme / caspase
Research Abstract

Hepatocyte growth factor (HGF), also known as the scatter factor and tumor cytotoxic factor, is a most potent mitogen for many epithelial cells and is suggested to support the process of normal development and tissue regeneration.
In this study, we first examined the induction of apoptosis in human junctional and gingival epithelial cells induced by serum deprivation, and investgated the protective effect of HGF against apoptosis of these cells. At present, we obtained following results :
1. When these cells were cultured in serum-free medium for 24h, the cells underwent apoptosis, judged by generation of oligonucleosomal fragmentation of nuclear DNA and by in situ detection of fragmented DNA by TUNEL method. However, DNA fragmentation was markedly inhibited when the cells were incubated with HGF (10 ng/ml) in serum-free medium.
2. We measured interleukin-1beta converting enzyme (ICE, named recently as caspase-1)-like protease activity in these cell extracts after incubation for 24h in serum-free medium and found that caspase-3 activity, but not caspase-1 activity, was increased about 2 times as compared with those of control cells incubated in the presence of 10% serum.
3. Specific inhibitor for caspase-3, acetyl-Asp-Glu-Val-Asp-aldehyde inhibited not only the activation of caspase-3 but also the DNA fragmentation induced by serum deprivation, suggesting that activation of caspase-3 is involved in induction of apoptosis in these cells by serum deprivation.
4. We examined the effect of HGF on the expression of Bcl-2, which is one of apoptosis suppressor proteins, by Western blotting analysis, and found that HGF increased the expression of Bcl-2.
These results suggest that serum deprivation induces apoptosis in human junctional and gingival epithelial cells by increasing caspase-3 activity and that HGF suppresses the apoptosis by increasing the expression of Bcl-2, followed by inhibiting caspase-3 activation.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Arakaki,N.,et al.: "Hepatocyte growth factor/scatter factor activates the apoptosis sinaling pathway by increasing caspase-3 activity in Sarcoma 180 cells" Biochem.Biophys.Res.Commun.245. 211-215 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arakaki,N.,et al.: "Involvement of Oxidative Stress in Tumor Cytotoxic Activity of Hepatocyte Growth Factor/Scatter Factor" J.Biol.Chem.(in press). (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naokatu Arakaki, Jamil Ahsan Kazi, Takehiro Kajihara, Tomokazu Ohnishi, and Yasushi Daikuhara: ""Hepatocyte growth factor/scatter factor activates the apoptosis sinaling pathway by increasing caspase-3 activity in Sarcoma 180 cells"" Biochem. Biophys. Res. Commun.245. 211-215 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naokatu Arakaki, Takehiro Kajihara, Rieko Arakaki, Tomokazu Ohnishi, Jamil Ahsan Kazi, Hideki Nakashima, andYasushi Daikuhara: ""Involvement of Oxidative Stress in Tumor Cytotoxic Activity of Hepatocyte Growth Factor/Scatter Factor"" J.Biol. Chem.(in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Arakaki,N.,et al.: "Hepatocyte groeth factr/scatter factor activates the apoptosis sinaling pathway by increasing caspase-3 activity in Sarcoma 180 cells" Biochem.Biophys.Res Commun.245. 211-215 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Arakaki,N.,et al.: "Involvement of Oxidative Stress in Cytotoxic Activity of Hepatocyte Growth Factor/Scatter Factor" J.Biol.Chem.(in press). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ohnishi,T.: "Eur.J.Biochem." Effect of phosphorylated rat fetuin on the growth of hepatocytes in primary culture in the presence of human hepatocyte-growth factor.243. 753-761 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 新垣 尚捷: "肝再生因子とシグナル伝達" BioClinica. 12. 863-867 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Harvey,P.: "Expression of HGF/SF in mesothelioma cell lines and its efffects on cell motility, proliferation and morphology." Br.J.Cancer. (in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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