2007 Fiscal Year Final Research Report Summary
Analysis of anti-platelet and anti-thrombotic effects of a neuron guidance molecule,semaphorin 3A
| Project/Area Number |
18599004
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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 |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
KASHIWAGI Hirokazu Osaka University, Graduate School of Medicine, Assistant Professor (10432535)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYAMA Yoshiaki Osaka University, Hospital, Associate Professor (80252667)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Platelet / Thrombosis / semaphoring 3A / signal transduction / PI3 kinase |
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| Research Abstract |
(1) Effects of Sena3A on thrombosis and atherosclerosis
To express large amount of Sema3A in vivo, we made Sema3A-adenovirus. We used an in vivo thrombosis model by irradiation of helium-neon laser to Evans blue injected mice. By monitoring the production of thrombosis under video-microscope, we analyzed effects of Sema3A on thrombosis production.
(2) Analysis of anti-platelet mechanism of Sema3A
To elucidate the inhibitory mechanism of platelet function by Sema3A, we investigated the impacts of Sema3A on platelet activating signaling induced by thrombin or convubxin. Sema3A did not affect thrombin-induced PKC activation. In contrast, Sema3A markedly inhibited P2Y_12 and PI3 kinase-dependent AKT activation induced by thrombin. Addition of excessive ADP could not restore the inhibition of AKT activation by Sema3A. Sema3A also inhibited thrombin-induced Rap1 activation, which appeared to be regulated by PI3 kinase activity. Sema3A inhibited not only thrombin but also convulxin-induced AKT and Rapl activation, whereas it did not affect convulxin-induced phosphorylation of LAT, SLP-76, PLC□2, or PKC substrates. These results suggested that irrespective of the type of agonists, Sema3A antagonizes PI3 kinase pathway induced by agonists in platelets.
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Research Products
(28 results)
