Hydrogen peroxide–induced apoptosis mediated by p53 protein in glial cells

✍ Scribed by Yoshihisa Kitamura; Takashi Ota; Yasuji Matsuoka; Ikuo Tooyama; Hiroshi Kimura; Shun Shimohama; Yasuyuki Nomura; Peter J. Gebicke-Haerter; Takashi Taniguchi

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 257 KB
• Volume: 25
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/(sici)1098-1136(19990115)25:2<154::aid-glia6>3.0.co;2-s

✦ Synopsis

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 (H2O2) caused cell death in a time- and concentration-dependent manner, accompanied by nucleosomal DNA fragmentation and chromatin condensation. After treatment with H2O2, p53 protein was highly expressed and protein levels of Bak, p21WAF1/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 H2O2-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 p21WAF1/CIP1 and GADD45, and that glial apoptosis caused by oxidative stress may be mediated by p53-induced Bak.