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Hydrogen peroxide–induced apoptosis mediated by p53 protein in glial cells
Author(s) -
Kitamura Yoshihisa,
Ota Takashi,
Matsuoka Yasuji,
Tooyama Ikuo,
Kimura Hiroshi,
Shimohama Shun,
Nomura Yasuyuki,
GebickeHaerter Peter J.,
Taniguchi Takashi
Publication year - 1999
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/(sici)1098-1136(19990115)25:2<154::aid-glia6>3.0.co;2-s
Subject(s) - hydrogen peroxide , biology , apoptosis , microbiology and biotechnology , neuroglia , p53 protein , programmed cell death , neuroscience , biochemistry , central nervous system
It is now generally accepted that massive neuronal death due to oxidative stress is a regular feature of brains in neurodegenerative diseases. However, much less attention has been given to the death of glial cells. In this study, we examined p53‐sensitive apoptosis of cells by using human glioblastoma A172 cells and p53 ‐deficient mouse astrocytes. In human A172 cells, hydrogen peroxide (H 2 O 2 ) caused cell death in a time‐ and concentration‐dependent manner, accompanied by nucleosomal DNA fragmentation and chromatin condensation. After treatment with H 2 O 2 , p53 protein was highly expressed and protein levels of Bak, p21 WAF1/CIP1 and GADD45 were also enhanced. However, the protein levels of Bcl‐2 and Bax did not change. On the other hand, primary cultured astrocytes from p53 ‐deficient mouse brain grew faster than wild‐type and heterozygous astrocytes. In addition, p53 ‐deficient astrocytes were more resistant to H 2 O 2 ‐induced apoptosis than wild‐type and heterozygous astrocytes. These results suggest that glial proliferation and the repair of damaged DNA may be regulated by p53‐induced p21 WAF1/CIP1 and GADD45, and that glial apoptosis caused by oxidative stress may be mediated by p53‐induced Bak. GLIA 25:154–164, 1999. © 1999 Wiley‐Liss, Inc.