title: 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.affiliation: Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. yama@anat2.med.osaka-u.ac.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Manabu
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Hori
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Nobuteru
authors.initials: N
authors.lastname: Tojo
authors.forename: Nobuya
authors.initials: N
authors.lastname: Matsuoka
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Miyake
authors.forename: Kousuke
authors.initials: K
authors.lastname: Kasai
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Michio
authors.initials: M
authors.lastname: Tamatani
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
authors.forename: Masaya
authors.initials: M
authors.lastname: Tohyama
mesh_terms: D000818:Animals; D016923:Cell Death; D002470:Cell Survival; D004268:DNA-Binding Proteins; D005786:Gene Expression Regulation; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D051741:Kruppel-Like Transcription Factors; D011494:Protein Kinases; D011506:Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D051741:Kruppel-Like Transcription Factors; C490820:PEG3 protein, human; C490821:Peg3 protein, rat; D011506:Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases