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Studies on the molecular mechanisms of carbon monoxide on the induction or protection of cell death.

Research Project

Project/Area Number 14570382
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Legal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

UEMURA Koichi  The University of Tokyo, Graduate School of Medicine, Reserch Associate, 大学院・医学系研究科, 助手 (30244586)

Co-Investigator(Kenkyū-buntansha) YOSHIDA Ken-ichi  The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40166947)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Keywordscarbon monoxide / ischemisa / reactive oxygen species / necrosis / apoptosis / calcium / HO-1 / H9c2 / 虚血細 / 虚血細胞死 / 活性酸素種
Research Abstract

Carbon monoxide (CO), either exogenous or endogenous, has been shown to protect the myocardial and vascular cells against injuries due to ischemia or lipopolysaccharide, through NF-kB or mitochondrial ATP-dependent K^+-channel. Heme-oxygenase (HO)-1, generates CO, thereby protecting the cells. We have shown that a Ca^<2+>-dependent protease calpain promotes necrotic death in the cardiogenic H9c2 cells under hypoxia through α-fodrin proteolysis (Aki, T., Yoshida, K., and Fujimiya, T. (2002) J.Biochem. 132, 921-926). Here, we show the first line of evidence that CO inhibits Ca^<2+>-influx, as detected by fluo-3 fluorescenece, which was enhanced by a L-type Ca^<2+>-channel agonist BAYK8644. The ischemic death was characterized as necrotic either by dye exclusion, LDH release, or propidium iodide permeabilization. The Ca^<2+>-influx, α-fodrin proteolysis, as detected by western blotting, and the ischemic death, were inhibited by CO ora L-type Ca^<2+.-channel inhibitor verapamil. Ischemia also induced mitochondrial depolarization, as detected by JC-1, which was inhibited by CO or verapamil. Additionally, reactive oxygen species (ROS) generation, as detected by DCF, hydroethidine, or Amplex Red Hydrogen Peroxide, was enhanced by ischemia, but unaffected by Co. Hemin treatment increased the HO-1 expression in the hypoxic cells, as detected by western blotting. The HO-1 induction reduced the Ca^<2+>-influx and cell death after ischemia. Thus, exogenous and endogenous CO protect the cardiomyogenic cells against ischemia by inhibiting Ca^<2+>-influx through L-type Ca^<2+> channel and calpain activation.

Report

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

    (7 results)

All Other

All Publications (7 results)

  • [Publications] K.Uemura, S.Hoshino, K.Uchida, R.Tsuruta, T.Maekawa, K.Yoshida.: "Hypothermia attenuates delayed cortical cell death and ROS generation following CO inhalation."Toxicology Letters. 145. 101-106 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 上村公一, 吉田謙一: "一酸化炭素中毒-基礎から臨床へ"日本医事新報. 4154. 23-28 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koichi Uemura, Sumihisa Hoshino, Koji Uchida, Ryosuke Tsuruta, Tsuyoshi Maekawa, Ken-ichi Yoshida: "Hypothermia attenuates delayed cortical cell death and ROS generation following CO inhalation"Toxicol.Lett.. 145(2). 101-106 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koichi Uemura, Ken-ichi Yoshida: "Carbon monoxide intoxiucation-from basic to clinical"Japan medical Journal(in Japanese). 4154. 23-28 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] K.Uemura, S.Hoshino, K.Uchida, R.Tsuruta, T.Maekawa, K.Yoshida: "Hypothermia attenuates delayed cortical cell death and ROS generation following CO inhalation."Toxicology Letters. 145. 101-106 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] 上村公一, 吉田謙一: "一酸化炭素中毒-基礎から臨床へ"日本医事新報. 4154. 23-28 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Koichi Uemura, Toshihiko Aki, Kazuhito Yamaguchi, Ken-ichi Yoshida: "Protein kinase C-e protects PC12 cells against methamphetamine-induced death : Possible involvement of suppression of glutamate receptor"Life Sciences. 75. 1595-1607 (2003)

    • Related Report
      2002 Annual Research Report

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

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