| Project/Area Number |
18590381
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Tokai University |
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Principal Investigator |
TAKEKOSHI Susumu Tokai University, School of Medicine, Associate Professor (70216878)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIZAWA Shunya Tokai Univ., School of Medicine, Associate Professor (70197234)
OSAMURA Yoshiyuki Tokai Univ., School of Medicine, Professor (10100992)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | protein kinase C / diacylglycerol / oxidative stress / lipid peroxidation / neuron / brain / signal transduction / PKC delta / protein kinase C / diacylglycerol / oxidative stress / lipid peroxidation / neuron / brain / signal transduction / MAP kinase |
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| Research Abstract |
It is well known that PKC plays a crucial role in receptor-mediated signal transduction affecting diverse range of cellular responses. We have demonstrated that oxidized-diacylglycerol (DAG-OOH) activates rat brain PKC as efficiently as phorbol ester (PMA), artificial and powerful activator for PKC. This result markedly suggested that DAG-OOH might act as a biological messenger in oxidative stress to efficiently alter the PKC-dependent signal transduction system to a similar extent to PMA. Furthermore, DAG-OOH injured the cultured neurons with the over-activation of PKC delta and MAP kinase. Among these studies, it has been suspected that two types of PKC isoforms (PKC-X: more susceptible to DAG-OOH than other PKC isoforms, PKC DSV: PKC delta splicing variant, which has only DAG binding domain but not kinase domain) exist in rat brain. PKC DSV is thought to act as a regulatory molecule for the DAG-OOH and PKC delta-induced neuronal cell injury. In the present study, the role of PKC DSV has been examined by means of the cells over-expressed the genes for PKC DSV, PKC delta and PKC alpha. In 2006, the adenovirus expression vectors for these genes were prepared. PC12 cells were transfected with these expression vectors. In 2007, PKC DSV-transfected cells were stimulated by the addition of PKC activator such as PMA. The growth signal induced by PMA irritation has been suppressed by the transfection of PKC DSV gene. These results suggested that PKC DSV regulate the over-activation of PKC delta provoked by DAG-OOH stimulation.
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