2005 Fiscal Year Final Research Report Summary
Study of the activation mechanism of small G-proteins and its effects on the pathology in cerebral infarction region.
| Project/Area Number |
16390069
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | Kitasato University |
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Principal Investigator |
SASAKI Yasuharu Kitasato Univ., School of Pharmaceutical sciences, professor, 薬学部, 教授 (90327445)
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| Co-Investigator(Kenkyū-buntansha) |
NAITO Yasuhito Kitasato Univ., School of Pharmaceutical sciences, assistant professor, 薬学部, 講師 (80303618)
MATSUO Yuri Kitasato Univ., School of Pharmaceutical sciences, research associate, 薬学部, 助手 (10306657)
TANABE Atsuhiro Kitasato Univ., School of Pharmaceutical sciences, research associate, 薬学部, 助手 (50365186)
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| Project Period (FY) |
2004 – 2005
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| Keywords | small G-protein / Rho-kinase / mPGS-1 / CaMKI / PGE_2 / brain ischemia / MARCKS |
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| Research Abstract |
1.Identification of a critical factor of rat stroke-reperfusion injury : The mRNA and protein of mPGES-1 are significantly induced in the infarct region after ischemia of MCAO rat and mouse models (The content of PGE_2 in ischemic cortex was about 10-fold higher than control cortex). The mPGES-1 induction occurred in neurons in the peri-infarct region and microglia and vascular endothelial cells in the ischemic core region of the cortex (submitted). Prier to this study, we confirmed that mPGES-1 is induced in an inflammatory region by injection of LPS (Matsuo-Ikeda et al. (2005) J Neurochem. 94 1546-1558)
2.The investigation of the role of mPGES-1 in postischemic insult ; a study using mPGES-1 knockout (KO) mice : The postischemic PGE_2 production was completely absent in the KO mice. Furthermore, the postischemic injury observed in WT mice was ameliorated in KO mice. The intracerebroventricular injections of PGE_2 significantly exaggerated the postischemic injury in KO mice to the same
… More
level as in the WT mice.
These results suggest that mPGES-1 is a critical factor of stroke-reperfusion injury.
3.Activation of rat astrocytes by lysophosphatidic acid (LPA) and involvement of Rho-kinase activation : Our study demonstrate that LPA induces morphological change in astrocytes through phosphorylation of MLC by Rho-kinase and actin reorganization.
4.Bradykinin stimulation and phorbol ester-activated PKC induced MARCKS phosphorylation in cultured neuroblastoma cells : This phosphorylation was mediated by small G-protein RhoA and its effector Rho-kinase at least in part as like as LPA stimulation (Tanabe et al. (2006) BBRC345 156-161).
5.Characterization of novel Ca/calmodulin dependent protein kinase I β2 (CaMKI β2) : Neuron specific CaMKI β2 is activated with Thr171 phosphorylation CaMKK and just immediately Thr304 and Ser305 were auto-phosphorylated to reduce the activity. This flip-flop mechanism in activity regulation is characteristic. Finally, CaMKI β2 was dephosphorylated and became to the inactive form. Less
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Research Products
(4 results)
