Peg3/Pw1 Is Involved in p53-mediated Cell Death Pathway in Brain Ischemia/Hypoxia
| Autor: | Kousuke Kasai, Osamu Hori, Toshihide Yamashita, Michio Tamatani, Nobuteru Tojo, Nobuya Matsuoka, Shin-ichi Miyake, Hisashi Sugimoto, Satoshi Ogawa, Manabu Taniguchi, Atsushi Yamaguchi, Masaya Tohyama |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Programmed cell death
Cell Survival Kruppel-Like Transcription Factors In situ hybridization Biology Biochemistry Rats Sprague-Dawley Brain ischemia Gene expression medicine Animals RNA Messenger Viability assay Molecular Biology Regulation of gene expression Cell Death Reverse Transcriptase Polymerase Chain Reaction Proteins Cell Biology Hypoxia (medical) medicine.disease Rats Cell biology DNA-Binding Proteins Gene Expression Regulation Cell culture Hypoxia-Ischemia Brain Cancer research Tumor Suppressor Protein p53 medicine.symptom Protein Kinases Transcription Factors |
| Zdroj: | Journal of Biological Chemistry. 277:623-629 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m107435200 |
| Popis: | Emerging evidence has shown that tumor suppressor p53 expression is enhanced in response to brain ischemia/hypoxia and that p53 plays a critical role in the cell death pathway in such an acute neurological insult. However the mechanism remains unclear. Recently it was reported that Peg3/Pw1, originally identified as a paternally expressed gene, plays a pivotal role in the p53-mediated cell death pathway in mouse fibroblast cell lines. In this study, we found that Peg3/Pw1 expression is enhanced in peri-ischemic neurons in rat stroke model by in situ hybridization analysis, where p53 expression was also induced by immunohistochemical analysis. Moreover, we found that p53 was co-localized with Peg3/Pw1 in brain ischemia/hypoxia by double staining analysis. In human neuroblastoma-derived SK-N-SH cells, Peg3/Pw1 mRNA expression is enhanced remarkably at 24 h post-hypoxia, when p53 protein expression was also enhanced at high levels. Subcellular localization of Peg3/Pw1 was observed in the nucleus. Adenovirus-mediated high dose p53 overexpression induced Peg3/Pw1 mRNA expression. Overexpression of Peg3/Pw1 reduced cell viability under hypoxic conditions, whereas that of the C-terminal-deleted mutant and anti-sense Peg3/Pw1 inhibited hypoxia-induced cell death. These results suggest that Peg3/Pw1 is involved in the p53-mediated cell death pathway as a downstream effector of p53 in brain ischemia/hypoxia. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|