Peg3/Pw1 is involved in p53-mediated cell death pathway in brain ischemia/hypoxia.

Abstract

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.

• Authors: Atsushi Yamaguchi, Manabu Taniguchi, Osamu Hori, Satoshi Ogawa, Nobuteru Tojo, Nobuya Matsuoka, Shin-ichi Miyake, Kousuke Kasai, Hisashi Sugimoto, Michio Tamatani, Toshihide Yamashita, Masaya Tohyama
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 277 Issue 1 Pg. 623-9 (Jan 04 2002) ISSN: 0021-9258 [Print] United States
• PMID: 11679586 (Publication Type: Journal Article)

Chemical References

• DNA-Binding Proteins
• Kruppel-Like Transcription Factors
• PEG3 protein, human
• Peg3 protein, rat
• Proteins
• RNA, Messenger
• Transcription Factors
• Tumor Suppressor Protein p53
• Protein Kinases

Topics

• Animals
• Cell Death
• Cell Survival
• DNA-Binding Proteins
• Gene Expression Regulation
• Hypoxia-Ischemia, Brain (metabolism, pathology)
• Kruppel-Like Transcription Factors
• Protein Kinases
• Proteins (analysis, genetics, physiology)
• RNA, Messenger (analysis)
• Rats
• Rats, Sprague-Dawley
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription Factors
• Tumor Suppressor Protein p53 (analysis, physiology)