Hydrogen peroxide-induced apoptosis mediated by p53 protein in glial cells.

Abstract:

: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.

journal_name

Glia

journal_title

Glia

authors

Kitamura Y,Ota T,Matsuoka Y,Tooyama I,Kimura H,Shimohama S,Nomura Y,Gebicke-Haerter PJ,Taniguchi T

subject

Has Abstract

pub_date

1999-01-15 00:00:00

pages

154-64

issue

2

eissn

0894-1491

issn

1098-1136

pii

10.1002/(SICI)1098-1136(19990115)25:2<154::AID-GLI

journal_volume

25

pub_type

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