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

Analyses for the function and related gene of humanin that suppresses cell death induced by mutant Alzheimer disease genes

Research Project

Project/Area Number 14570612
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNara Medical University

Principal Investigator

UENO Satoshi  Nara Medical University, Dept.Neurology, Professor, 医学部, 教授 (40184949)

Co-Investigator(Kenkyū-buntansha) HIRANO Makito  Nara Medical University, Dept.Neurology, Assistant Professor, 医学部, 講師 (50347548)
MURATA Ken-ya  Nara Medical University, Dept.Neurology, Assistant Professor, 医学部, 講師 (90264853)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsHumanin / apoptosis / mitochondrial disease / ミトコンドリア病 / ヒューマン / 神経細胞死
Research Abstract

Humanin (FIN) is a 24-amino-acid peptide that protects cells from apoptosis induced by mutant Alzheimer's disease (AD) genes, but its protective effect against other cytotoxic factors remains unclear. The aim of this project is to establish the therapeutic potential of HN for various diseases or types of cell death other than AD. The effect on non-specific neuronal cell death was tested using rat pheochromocytoma PC12 cells undergoing apoptosis after serum deprivation. HN significantly decreased cell death and fragmentation of nuclear DNA with the suppression of caspase 3 activity. To further extend the applicability of FIN, we examined human lymphocytes cultured under serum-deprived condition. FIN increased ATP level and suppressed cell death, suggesting that this peptide may be used for the treatment of disorders with ATP deficiency, such as Parkinsons disease and mitochondrial diseases (MDs). Therefore, we tested FIN in mitochondrial encephalopathy, lactic acidosis, and stroke-like … More episodes (MELAS), one of the most common MDs. Readily obtainable peripheral lymphocytes from patients with MELAS were cultured under serum-deprived condition, which significantly decreased the ATP levels in MELAS cells compared with those in controls. FIN increased the ATP levels, and suppressed cell death and mitochondrial DNA copy number. Similar cytoprotective and ATP-producing effects were observed in human neuroblastoma SK-N-MC cells and rhabdomyosarcoma TE671 cells, suggesting that FIN may alleviate the impairment in brain and muscle, which are the tissues predominantly involved in MELAS because of high ATP demand. Apoptosis may be a defense mechanism to remove cells with increased abnormal mitochondria in response to ATP deficiency and formation of reactive oxygen species, however, it may disturb cellular function, leading to further tissue damages in MELAS. HN breaks this vicious circle, and therefore, it is a promising therapeutic candidate for MDs. In conclusion, we have provided experimental evidence for the broader therapeutic spectrum of HN. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] 仮屋眞吾: "Humanin inhibits cell death of serum-deprived PC12h cells."Neuroreport. 13. 903-907 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 仮屋眞吾: "Humanin may provide therapeutic tool for mitochondria-related diseases by accelerating transcription activity of mitochondria DNA."Ann Neurol. 52. S89 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 高橋信行: "Two novel spliced presenilin 2 transcripts in human lymphocyte with oxidant stress and brain."Mol Cell Biochem.. 252. 279-283 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 仮屋眞吾: "Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes."Mol Cell Biochem.. 254. 83-89 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 仮屋眞吾: "Humanin improves bioenergetic state of cells harboring A3243G mitochondrial DNA mutation."Ann Neurol. 54. S46 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 仮屋眞吾: "無血清培養により誘導されるアポトーシスと,Humaninによる細胞死抑制"奈良医学雑誌. 54. 271-272 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariya S: "Humanin inhibits cell death of serum-deprived PC12h cells"Neuroreport. 13. 903-907 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariya S: "Humanin may provide therapeutic tool for mitochondria-related diseases by accelerating transcription activity of mitochondria DNA"Ann Neurol. 52. S89 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Takahashi N: "Two novel spliced presenilin 2 transcripts lymphocyte in human with oxidant stress and brain"Mol Cell Biochem. 252. 279-283 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariya S: "Humanin Improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes"Mol Cell Biochem. 254. 83-89 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kariya S: "Humanin improves bioenergetic state of cells harboring A3243G mitochondrial DNA mutation"Ann Neurol. 54. S46 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Shingo Kariya: "Humanin improves impaired metabolic activity and prolongs survival of serum-deprived human lymphocytes"Molecular and Cellular Biochemistry. 254・1-2. 83-89 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Shingo Kariya: "Humanin improves bioenergetic state of cells harboring A3243G mitochondrial DNA mutation"Annals of Neurology. 54・supple 7. S46 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Singo Kariya: "Humanin inhibits cell death of serum-deprived PC12 cells"Neuroreport. 13・6. 903-907 (2002)

    • Related Report
      2002 Annual Research Report

URL: 

Published: 2002-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi