Functional Proteins Involved in Regulation of Intracellular Ca^<2+> for Drug Development : Role of Calcium/Calmodulin-Dependent Protein Kinases in Ischemic Neuronal Death
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概要
- 論文の詳細を見る
Excessive elevation of intracellular calcium level seems to be a trigger of ischemic neuronal injury. Calcium/calmodulin (CaM)-dependent protein kinase kinase (CaM-KK) is an upstream kinase for CaM kinase IV (CaM-KIV) that was reported to prevent apoptosis through phosphorylation of CREB (cyclic AMP responsive element-binding protein). We here observed that CaM-KK could directly activate Akt, thereby preventing apoptosis in cultured cells. Then we examined changes in Akt and CaM-KIV activities in gerbil forebrain ischemia. In 5-min-ischemia-caused delayed neuronal death in hippocampal CA1 neurons, Akt and CaM-KIV activities were decreased after reperfusion. On the other hand, during induction of ischemic tolerance, Akt activity gradually and persistently increased in the CA1 neurons with transient increase in CREB phosphorylation. Inhibition of Akt activity with wortmannin or CREB-DNA binding with CRE-decoy injection resulted in failure of generation of ischemic tolerance. These results indicated activation of Akt and CaM-KIV play important roles in induction of the ischemic tolerance. Activation of CaM-KK may provide a new strategy for overcoming the ischemic stress.
- 社団法人 日本薬理学会の論文
- 2005-03-20
著者
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Fukunaga Kohji
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Japan
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KURATSU Jun-ichi
Department of Neurosurgery, Kumamoto University Medical School
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YANO Shigetoshi
Department of Neurosurgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University Grad
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MORIOKA Motohiro
Department of Neurosurgery, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University Grad
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Kuratsu Jun-ichi
Department Of Neurosurgery Faculty Of Medical And Pharmaceutical Sciences Kumamoto University Gradua
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Kuratsu Jun-ichi
Department Of Neurosurgery Graduate School Of Medical Sciences Kumamoto University
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Kuratsu Jun-ichi
Department Of Neurosurgery Faculty Of Medical And Pharmaceutical Sciences Kumamoto University
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Kuratsu Jun-ichi
Department Of Neurosurgery Kumamoto University School Of Medicine
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Fukunaga Kohji
Tohoku Univ. 21st Century Coe Program “crescendo" Jpn
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Fukunaga K
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University
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Fukunaga Kohji
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Tohoku University
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Kuratsu Jun-ichi
Department Of Neurosurgery Shimonoseki Kosei Hospital
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Yano Shigetoshi
Department Of Neurosurgery Faculty Of Medical And Pharmaceutical Sciences Kumamoto University Gradua
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Yano Shigetoshi
Department Of Neurosurgery Kumamoto University School Of Medicine
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Morioka Motohiro
Department Of Neurosurgery Faculty Of Medical And Pharmaceutical Sciences Kumamoto University Gradua
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Morioka Motohiro
Department Of Neurosurgery Graduate School Of Medical Sciences Kumamoto University
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Yano Shigetoshi
Department Of Diagnostic Radiology Graduate School Of Medical Sciences Kumamoto University
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Shigematsu Yoshinori
Department Of Radiology Kumamoto University School Of Medicine
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Kuratsu Jun-ichi
Department Of Neurosurgery Faculty Of Medical And Pharmaceutical Sciences Kumamoto University Gradua
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