Analysis of anti-platelet and anti-thrombotic effects of a neuron guidance molecule,semaphorin 3A

神经元引导分子信号蛋白3A的抗血小板和抗血栓作用分析

• 批准号: 18599004
• 负责人: KASHIWAGI Hirokazu
• 金额: $ 2.46万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18599004/
• 关键词: Platelet; Thrombosis; semaphoring 3A; signal transduction; PI3 kinase; semaphoring 3A

(1) Effects of Sena3A on thrombosis and atherosclerosisTo 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 Sema3ATo 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.

(1)Sena3A对血栓形成和动脉粥样硬化的影响为了在体内大量表达Sema3A，我们制备了Sema3A-腺病毒。我们用氦-霓激光照射伊文思蓝注射的小鼠体内血栓形成模型。通过视频显微镜监测血栓形成，分析Sema3A对血栓形成的影响。(2)Sema3A抗血小板机制为阐明Sema3A抑制血小板功能的机制，我们研究了Sema3A对凝血酶或凝血酶诱导的血小板活化信号的影响。Sema3A不影响凝血酶诱导的PKC激活。而Sema3A则能显著抑制凝血酶诱导的依赖于P2Y_12和PI3的AKT的激活。过量ADP不能恢复Sema3A对AKT激活的抑制作用。Sema3A还抑制凝血酶诱导的Rap1激活，这似乎是由PI3激酶活性调节的。Sema3A不仅抑制凝血酶，而且抑制惊厥毒素诱导的AKT和RAPL激活，但不影响惊厥毒素诱导的LAT、SLP-76、PLC-2或PKC底物的磷酸化。这些结果表明，无论激动剂的类型如何，Sema3A都能拮抗激动剂诱导的血小板PI3激酶通路。

项目成果

Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura

• DOI: 10.1182/blood-2005-07-2765
• 发表时间: 2006-04-15
• 期刊: BLOOD
• 影响因子: 20.3
• 作者: Banno, F;Kokame, K;Miyata, T
• 通讯作者: Miyata, T

P2Y_<12>-independent transient activation and P2Y_<12>-dependnet prolonged activation of platelet integrin α_IIbβ_3.

血小板整联蛋白α_IIbβ_3的P2Y_ 12 依赖性瞬时激活和P2Y_ 12 依赖性延长激活。

• 发表时间: 2006
• 作者: Shiraga M;et. al.
• 通讯作者: et. al.

Critical role of ADP interaction with P2Y receptor in the maintenance of αIIbβ3 activation: association with Rap1B activation

ADP 与 P2Y 受体相互作用在维持 αIIbβ3 激活中的关键作用：与 Rap1B 激活的关联

• 发表时间: 2006
• 期刊: Journal of Thrombosis and Haemostasis 4
• 作者: Kamae T;et. al.
• 通讯作者: et. al.

Four cases of pseudothrombocytopenia due to platelet cold agglutinins

血小板凝集素所致假性血小板减少症4例

• 发表时间: 2006
• 期刊: Rinsho Ketsueki [Japanese] 47
• 作者: Kurata;Y;et. al.
• 通讯作者: et. al.

血栓形成のメカニズムup-to-date

最新血栓形成机制

• 发表时间: 2007
• 期刊: Angiology Frontier 6(3)
• 作者: 高田由香;金地泰典;諸井将明;関律子;奥英二郎;佐野雅之;中里幸恵;緒方秀章;吉本幸治;薬師寺和昭;橋口道俊;今村理恵;大崎浩一;大坪惟範;森重聡;出原賢治;末岡榮三朗;今村豊;岡村孝;冨山佳昭
• 通讯作者: 冨山佳昭