Neurochemical Research

, Volume 31, Issue 1, pp 21–32

Neuroprotective Effect of A20 on TNF-Induced Postischemic Apoptosis

  • Luyang Yu
  • Hongsheng Miao
  • Yanan Hou
  • Bao Zhang
  • Lihe Guo
Article

Focal cerebral ischemia causes apoptosis in neural cells during the postischemia period. TNF is critically involved in such neuronal apoptosis mediated by caspase pathways. A20 can inhibit TNF-induced apoptosis in many cell types. However, little work has been carried out in central nervous system. In the present study, gene transfer of A20 resulted in reduction of infarct volume and improvement of neurological deficit in ischemia rats. Results of flow cytometry, TUNEL and DNA fragmentation assay all indicated A20 could inhibit TNF-induced apoptosis both in primary rat hippocampal neurons and SH-SY5Y cells. Moreover, we found A20 targeted the TNF apoptotic pathway by inhibiting proteolytic cleavage of caspase 8 and 3 in SH-SY5Y cells. These data demonstrated A20 could effectively protect neurons from postischemic apoptosis and may function partly on death receptor caspase pathway. Gene transfer of A20 may be a promising approach to gene therapy for cerebral ischemia in the future.

Keywords

A20 gene TNF-α apoptosis focal cerebral ischemia 

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Luyang Yu
    • 1
    • 2
  • Hongsheng Miao
    • 1
  • Yanan Hou
    • 1
    • 2
  • Bao Zhang
    • 1
    • 2
  • Lihe Guo
    • 1
  1. 1.Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  2. 2.Graduate School of the Chinese Academy of SciencesChina

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