Role of phospholipid molecular species containing poly unsaturated fatty acids

含有多不饱和脂肪酸的磷脂分子种类的作用

• 批准号: 04453130
• 负责人: KITO Makoto
• 金额: $ 4.67万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04453130/
• 关键词: Arachidonic acid; Phospholipids; Collagen; Human platelets; 小胞体プロテアーゼ; ER-60プロテアーゼ; タンパク質代謝; ホスファチジルイノシトール; ホスファチジルセリン

We have indicated that several nanomolar thromboxane A_2 (TXA_2) originating from inositollipids may directly cause Ca^<2+> mobilization in human platelets during activation with collagen.The mechanism of arachidonic acid (AA) release in collagen-activated human platelets was studied. An arachidonic acid metabolite, thromboxane B_2, was formed in parallel with the formation of phosphatidic acid without fomation of lysophosphatidic acid or lysophosphatidylinositol in the absence of extracellular Ca^<2+>, suggesting that AA was released from PI via a PI-specific phospholipase C/diacylglycerol lipase/monoacylglycerol lipase pathway under the cytosolic low Ca^<2+> concentrations. Moreover, solubilized DG lipase and MG lipase could hydrolyze the substrates at basel cytosolic free Ca^<2+> concentrations. Subsequently, the relationship of cytosolic free Ca^2 concentrations and formation of AA metabolites was analyzed using Ca^<2+> ionophore, A23187. Collagen was able to induce a release of small amounts of AA under basal cytosolic Ca^<2+> conditions. However, a release of large amounts of AA was induced by phospholipase A_2 activated by both collagen-receptor occupancy and elevated Ca^<2+> levels. A TXA_2 mimetic agonist, STA_2 induced all the responses except for AA release. From these results, the mechanism of AA release and signal transduction in collagen-activated human platelets is discussed.

我们研究了人血小板在胶原活化过程中，几个纳摩尔的肌醇脂类来源的血栓素A_2（TXA_2）可直接引起血小板内Ca^<2+>的流动，并探讨了胶原活化血小板中花生四烯酸（AA）释放的机制。在缺乏细胞外Ca^2+时，花生四烯酸代谢产物血栓烷B_2与磷脂酸的形成同时生成，但不生成溶血磷脂酸或溶血磷脂酰肌醇，表明在胞浆Ca^2+浓度较低时，花生四烯酸通过磷脂酶C/甘油二酯脂肪酶/甘油单酯脂肪酶途径从磷脂酰肌醇中释放。可溶性DG脂肪酶和MG脂肪酶在巴塞尔内游离Ca^2+浓度基本不变的情况下也能水解底物。随后，利用Ca^2+离子载体A23187分析了胞浆游离Ca ^2浓度与AA代谢产物形成的关系。胶原蛋白能够在基础胞浆Ca^<2+>条件下诱导少量AA的释放。然而，大量AA的释放是由磷脂酶A_2诱导的，磷脂酶A_2被胶原受体占据和升高的Ca^<2+>水平激活。TXA_2模拟激动剂STA_2可诱导除AA释放外的所有反应。根据这些结果，讨论了胶原活化的人血小板中AA释放和信号转导的机制。

项目成果

R.Urade: "Inhibition by acidic phospholipids of protein degradation by ER-60 protease,a novel cysteine protease,of endoplasmic reticulum" FEBS Letters. 312. 83-86 (1992)

R.Urade：“酸性磷脂对内质网 ER-60 蛋白酶（一种新型半胱氨酸蛋白酶）蛋白质降解的抑制”FEBS Letters。

鬼頭 誠: "生体膜リン脂質の多機能性に関する生化学的研究" 日本農芸化学会誌. 67. 1047-1053 (1993)

Makoto Kito：“生物膜磷脂多功能性的生化研究”日本农业化学学会杂志 67. 1047-1053 (1993)。

R.Urade: "Inhibition by acidic phospholipids of protein degradation by ER-60 protease, a novel cysteine protease, of endoplasmic reticulum" FEBS Letters. 312(1). 83-86 (1992)

R.Urade：“酸性磷脂对内质网 ER-60 蛋白酶（一种新型半胱氨酸蛋白酶）蛋白质降解的抑制”FEBS Letters。

R.Urade: "Protein Degradation by ERp72 from Rat and Mouse Liver Endoplasmic Reticulum" J.Biol.Chem.268(29). 22004-22009 (1993)

R.Urade：“ERp72 对大鼠和小鼠肝脏内质网的蛋白质降解”J.Biol.Chem.268(29)。

R.Urade: "Protein Degradation by the Phosphoinositide-specific Phospholipase C-α Family from Rat Liver Endoplasmic Reticulum" J.Biol.Chem.267. 15152-15159 (1992)

R.Urade：“大鼠肝内质网中磷酸肌醇特异性磷脂酶 C-α 家族的蛋白质降解”J.Biol.Chem.267 (1992)。