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Role of mitochondria in neuron apoptosis during ischemia-reperfusion injury

  • Duan Qiuhong
  • Wang Ximing
  • Wang Zhongqiang
  • Lu Tao
  • Han Yixiang
  • He Shanshu
Article

Summary

To investigate the role of mitochondria in neuronal apoptosis, ischemia-reperfusion mediated neuronal cell injury model was established by, depriving of glucose, serum and oxygen in media. DNA fragmentation, cell viability, cytochrome C releasing, caspase3 activity and mitochondrial transmembrane potential were observed after N2a cells suffered the insults. The results showed that N2a cells in ischemic territory exhibited survival damage, classical cell apoptosis change, DNA ladder and activation of caspase3. Apoptosis-related alterations in mitochondrial functions, including release of cytochrome C and depression of mitochondrial transmembrane potential (ΔΓm) were testified in N2a cells after mimic ischemia-reperfusion. Moreover, activation of caspase3 occurred following the release of cytochrome C. However, the inhibitor of caspase3, Ac-DEVD-CHO, couldn't completely rescue N2a cells from apoptosis. Administration, of cyclosporine A, an inhibitor of mitochondria permeability transition pore only partly inhibited caspase3 activity and reduced DNA damage. Interestingly, treatment of Z-IETD-FMK, an inhibitor of caspase8 could completely reverse DNA fragmentation, but can't completely inhibit caspase3 activity. It was concluded that there were caspase3 dependent and independent cellular apoptosis pathways in N2a cells suffering ischemia reperfusion insults. Mitochondria dysfunction may early trigger apoptosis and amplify apoptosis signal.

Key words

mitochondrial ischemia-reperfusion apoptosis neuron cytochrome C 

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Copyright information

© Springer 2004

Authors and Affiliations

  • Duan Qiuhong
    • 1
  • Wang Ximing
    • 1
  • Wang Zhongqiang
    • 1
  • Lu Tao
    • 1
  • Han Yixiang
    • 1
  • He Shanshu
    • 1
  1. 1.Department of Biochemistry and Molecular Biolgy, School of Basic Medical SciencesHuazhong University of Science and TechnologyWuhanChina

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