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

2007 Fiscal Year Final Research Report Summary

Oxidative and endoplasmic reticulum stress in absence epilepsy

Research Project

Project/Area Number 18590078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Biological pharmacy
Research InstitutionNihon University

Principal Investigator

ISHIGE Kumiko  Nihon University, College of Pharmacy, Associate Professor (40212873)

Project Period (FY) 2006 – 2007
Keywordsabsence epilepsy / lethargic mouse / thalamus / oxidative stress / endonlasmic reticulum (ER) stress
Research Abstract

In order to characterize absence epilepsy-associated increases in endoplasmic reticulum (ER) stress-induced celluar damege in lethargic(Ih/Ih)mice, a genetic model of absence epilepsy, responsible pathways involved in the ER stress-induced cell death in the brain were compared between lethargic and control mice. The wet weight of the thalamus in lethargic mouse was lower than that in control mouse. The thalamus has been shown to play an important role in the absence epilepsy. The level of glucose regulated protein (GRP)78, ER chaperons, and activity of c-jun-N-terminal kinase (JNK), phospho-JNK/JNK in the thalamus of lethargic mouse higher than that of control mouse. These data suggested that ER stress was induced in the thalamus in a model of absence epilepsy.
In order to elucidate underlying mechanism of cell injury pathways, ER stress (tunicamycine ; TM)- and oxidative stress (H_2O_2 and 4-hydroxy-2-nonenal ; HNE)-induced cell injury pathways were investigated in HT22 cells, a mouse hippocampal cell line. Treatment with TM, H_2O_2 and HNE decreasedthecell viability in a time-and concentration-dependent manner. GADD153/C/EBP homologous protein (CHOP) was significantly induced after exposure to TM. In contrast, expression of caspase-12, ER stress-specific caspase, was not affected by TM. In the cells treated with H_2O_2, significant increases in the immunoreactivities of DJ-1 and nuclear factor-kB (NF-kB) subunits were observed in the nuclear fraction. H2O2 also induced an increase in the intracellular concentration of Ca^<2+> and cobalt chloride, a Ca^<2+> channel inhibitor, suppressed the H_2O_2-induced cell death. In HNE-treated cells, none of these phenomena were observed ; however, HNE adduct proteins were formed after exposure to HNE, but not to H_2O_2.
Further experiments are needed to ascertain whether the details of responsible pathways involved in the ER and oxidative stress in absence epilepsy.

  • Research Products

    (4 results)

All 2008 2007

All Journal Article (2 results) (of which Peer Reviewed: 1 results) Presentation (2 results)

  • [Journal Article] Comparative study of hydrogen peroxide-and 4-hydroxy-2-nonenal-induced cell death in HT22 cells2008

    • Author(s)
      Ishimura A, Ishige K, Taira T, Shimba S, Ono S, Ariga H, Tezuka M, Ito Y
    • Journal Title

      Neurochem Int. 52

      Pages: 776-785

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Comparative study of hydrogen peroxide-and 4-hydroxy-2-nonenal induced cell death in HT22 cells.2008

    • Author(s)
      Ishimura, A., Ishige, K., Taira, T., Shimba, S., Ono, S., Ariga, H., Tezuka, M., Ito, Y
    • Journal Title

      Neurochem Int 52

      Pages: 776-785

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] HT22細胞における4-hydroxy-2-nonenalの細胞死誘発機構2007

    • Author(s)
      伊藤 芳久、石村 淳、石毛 久美子、小菅 康弘
    • Organizer
      第34回日本トキシコロジー学会学術年会
    • Place of Presentation
      東京
    • Year and Date
      2007-06-28
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] The mechanisms of HNE-induced cell death in HT22 cells2007

    • Organizer
      The 34th Annual Meeting of Japanese Society of Toxicology
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-06-28
    • Description
      「研究成果報告書概要(欧文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi