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Hydrogen peroxide-induced apoptosis mediated by p53 protein in glial cells
Y Kitamura1, T Ota, Y Matsuoka
1Department of Neurobiology, Kyoto Pharmaceutical University, Japan.
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.
Insights
Oxidative stress induces glial cell death via p53-sensitive apoptosis. This study reveals p53 regulates glial proliferation and DNA repair, and mediates glial apoptosis through Bak.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Oxidative stress is a known contributor to neuronal death in neurodegenerative diseases.
- Glial cell death, a less-studied aspect, also plays a role in these conditions.
- The role of the p53 protein in glial cell apoptosis and proliferation requires further investigation.
Purpose of the Study:
- To investigate p53-sensitive apoptosis in glial cells under oxidative stress.
- To explore the role of p53 in regulating glial cell proliferation and DNA repair.
- To elucidate the molecular mechanisms underlying p53-mediated glial cell death.
Main Methods:
- Utilized human glioblastoma A172 cells and p53-deficient mouse astrocytes.
- Induced oxidative stress using hydrogen peroxide (H2O2).
- Assessed cell death, DNA fragmentation, chromatin condensation, and protein expression levels (p53, Bak, p21WAF1/CIP1, GADD45, Bcl-2, Bax).
Main Results:
- Hydrogen peroxide induced time- and concentration-dependent cell death in A172 cells, with increased p53, Bak, p21WAF1/CIP1, and GADD45 expression.
- p53-deficient astrocytes exhibited faster growth and increased resistance to H2O2-induced apoptosis compared to wild-type and heterozygous astrocytes.
- Bcl-2 and Bax protein levels remained unchanged in H2O2-treated A172 cells.
Conclusions:
- p53 plays a critical role in regulating glial cell proliferation and DNA repair, potentially via p21WAF1/CIP1 and GADD45.
- p53-mediated apoptosis of glial cells under oxidative stress appears to involve the Bak protein.
- These findings highlight the significance of p53 in glial cell responses to oxidative damage.