2010 Fiscal Year Final Research Report
Molecular mechanisms of particular defense system against oxidative stress induced by the control of signaling
| Project/Area Number |
20590385
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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, 医学部, 准教授 (70216878)
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| Co-Investigator(Kenkyū-buntansha) |
TAKIZAWA Shunnya 東海大学, 医学部, 教授 (70197234)
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| Co-Investigator(Renkei-kenkyūsha) |
OSAMURA Yoshiyuki 国際医療福祉大学, 大学院, 教授 (10100992)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 細胞 |
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| Research Abstract |
Protein kinase C (PKC) is a key molecule for intercellular signaling pathway in physiological conditions. PKC is an enzyme which is activated by calcium ion and lipids such as phosphatidylserine and 1,2-diacylglycerol (DAG). In recent years, many evidences that lipid peroxidation participates in intracellular signal transduction in physiology and pathology of aerobic organisms have been presented. We further demonstrated that 1,2-diacylglycerol hydroperoxide (oxidized-DAG) activated rat brain PKC as efficiently as phorbol ester, powerful artificial PKC activator . In this study, to elucidate the mechanism of novel and specific defence system against aberrant over-activation of PKC signaling by oxidized-DAG and subsequent to cell injury, we observed oxidized-DAG content and the expression of PKC δ SV (which is PKC δ splicing variant and may be considered as a dominant negative mutant of PKC δ molecule) in two animal models such as carbon tetrachloride (CCl4)-treated rat liver and ischemia-reperfusion (IR)-injured rat brain. In addition, the protective effects of PKC δ SV on oxidative stress were analyzed using PKCδ SV over-expressed PC12 cell. Oxidized DAG was significantly increased in both models. PKC δ SV was barely detected in normal and carbon tetrachloride-treated rat liver. On the other hands, PC12 cells over-expressing PKC SV resistant to over-activation of PKC signaling. These results suggested that oxidized-DAG is a key molecule for oxidative stress and PKC δ SV may have a specific function for the protection of oxidative stress caused by oxidized DAG.
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