Decreased Akt Activity is Associated with Activation of Forkhead Transcription Factor after Transient Forebrain Ischemia in Gerbil Hippocampus
-
- Takayuki Kawano
- Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto, Japan
-
- Motohiro Morioka
- Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan
-
- Shigetoshi Yano
- Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan
-
- Jun-ichiro Hamada
- Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan
-
- Yukitaka Ushio
- Department of Neurosurgery, Kumamoto University School of Medicine, Kumamoto, Japan
-
- Eishichi Miyamoto
- Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto, Japan
-
- Kohji Fukunaga
- Department of Pharmacology, Kumamoto University School of Medicine, Kumamoto, Japan
この論文をさがす
抄録
<jats:p>The authors recently reported that sodium orthovanadate rescues cells from delayed neuronal death in gerbil hippocampus after transient forebrain ischemia through phosphatidylinositol 3-kinase-protein kinase B (Akt) pathway ( Kawano et al., 2001 ). In the current study, they demonstrated that the activation of FKHR, a Forkhead transcription factor and a substrate for Akt, preceded delayed neuronal death in CA1 regions after transient forebrain ischemia. Adult Mongolian gerbils were subjected to 5-minute forebrain ischemia. Immunoblotting analysis with anti—phospho-FKHR antibody showed that phosphorylation of FKHR at serine-256 in the CA1 region decreased immediately after and 0.5 and 1 hour after reperfusion. The dephosphorylation of FKHR was correlated with the decreased Akt activity. Intracerebroventricular injection of orthovanadate 30 minutes before ischemia inhibited dephosphorylation of FKHR after reperfusion, and blocked delayed neuronal death in the CA1 region. Gel mobility shift analysis using nuclear extracts from the CA1 region prepared immediately after reperfusion revealed increases in DNA binding activity for the FKHR-responsive element on the Fas ligand promoter. The orthovanadate injection administered before ischemia inhibited its binding activity. Two days after reperfusion, expression of Fas ligand increased in the CA1 region and the orthovanadate injection inhibited this increased expression. These results suggest that the inactivation of Akt results in the activation of FKHR and, in turn, relates to the expression of Fas ligand in the CA1 region after transient forebrain ischemia.</jats:p>
収録刊行物
-
- Journal of Cerebral Blood Flow & Metabolism
-
Journal of Cerebral Blood Flow & Metabolism 22 (8), 926-934, 2002-08
SAGE Publications
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1361418519050521600
-
- NII論文ID
- 30009335654
-
- NII書誌ID
- AA10458430
-
- ISSN
- 15597016
- 0271678X
- http://id.crossref.org/issn/0271678X
-
- データソース種別
-
- Crossref
- CiNii Articles