Hydrogen peroxide-induced apoptosis mediated by p53 protein in glial cells.
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.
Kitamura
Y
Y
Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
Ota
T
T
Matsuoka
Y
Y
Tooyama
I
I
Kimura
H
H
Shimohama
S
S
Nomura
Y
Y
Gebicke-Haerter
P J
PJ
Taniguchi
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001932:Brain Neoplasms / Q000473:pathology / Q000648:ultrastructure; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage / Q000502:physiology; D053938:DNA Fragmentation / Q000187:drug effects; D005909:Glioblastoma / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009457:Neuroglia / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress / Q000502:physiology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D016877:Oxidants; D016159:Tumor Suppressor Protein p53; D006861:Hydrogen Peroxide