Peg3/Pw1 is involved in p53-mediated cell death pathway in brain ischemia/hypoxia.
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.
Yamaguchi
Atsushi
A
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
Taniguchi
Manabu
M
Hori
Osamu
O
Ogawa
Satoshi
S
Tojo
Nobuteru
N
Matsuoka
Nobuya
N
Miyake
Shin-ichi
S
Kasai
Kousuke
K
Sugimoto
Hisashi
H
Tamatani
Michio
M
Yamashita
Toshihide
T
Tohyama
Masaya
M
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*
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