The regulatory effects of ubiquitin-proteasome pathways on Fas-mediated apotosis

泛素-蛋白酶体途径对Fas介导的细胞凋亡的调节作用

• 批准号: 13670740
• 负责人: HANO Takuzo
• 金额: $ 2.3万
• 依托单位: Wakayama Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670740/
• 关键词: Apoptosis; Fas-Fas ligand signal; Proteasome; Oxidized LDL; Endothelium; Vascular smooth muscle cells; Fas-Fas ligandシグナル伝達系

We examined the effect of ubiquitin-proteasome pathway on both the expression of either Fas or Fas-related mRNA and sensitization of Fas-mediated apoptosis. Furthermore, we examined the clinical significance of Fas-mediated apoptosis, especially focused on acute coronary syndrome. The results are as follows. Experimental study: 1)The ubiquitin-proteasome pathway are involved in the susceptibility of Fas-mediated apoptosis in both cultured human vascular smooth muscle cells (VSMCs) and endothelial cells (ECs). That is, the up-regulation of surface Fas induced by the inhibition of proteasome activity leads to the sensitization of Fas-mediated apoptosis. Clinical study: 1)The patients with acute coronary syndrome had higher concentrations in both soluble FasL in peripheral blood and membrane FasL on monocytes than those of either healthy volunteers or the patients with stable angina. 2)There had no correlations of the concentrations between soluble FasL and membrane FasL, which suggests that both are regulated by different mechanisms. In conclusions. 1)Fas-niediated apoptosis in both VSMCs and ECs, at least in vitro, is regulated by ubiquitin-proteasome pathway. 2)Fas-FasL signal transduction may be related to the pathphysiolgy of acute coronary syndrome.

我们检查了泛素 - 蛋白酶体途径对FAS或FAS相关mRNA的表达以及FAS介导的细胞凋亡的敏化的影响。此外，我们研究了FAS介导的细胞凋亡的临床意义，尤其是针对急性冠状动脉综合征。结果如下。实验研究：1）泛素 - 蛋白酶体途径参与了培养的人血管平滑肌细胞（VSMC）和内皮细胞（ECS）中FAS介导的凋亡的敏感性。也就是说，抑制蛋白酶体活性引起的表面FA的上调导致FAS介导的凋亡的敏化。临床研究：1）急性冠状动脉综合征患者的外周血和膜FASL的浓度高于单核细胞的膜FASL，而健康的志愿者或稳定的心绞痛患者的浓度均高。 2）可溶性FASL和膜FASL之间的浓度没有相关性，这表明两者都受不同的机制调节。在结论中。 1）VSMC和EC的FAS脱凋亡，至少在体外受到泛素 - 蛋白酶体途径的调节。 2）FAS-FASL信号转导可能与急性冠状动脉综合征的途径有关。

项目成果

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Imanishi T、Hano T 等人：“血管紧张素 II 增强 VEGF 诱导的增殖和内皮祖细胞网络的形成。”高血压研究。

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Imanishi T, Hano T, Matsuo Y, Nishio I: "Oxidized LDL Inhibits vascular endothelial growth factor-induced endothelial progenitor cell differentiation"Clin Exp Pharmacol Physiol. 30(9). 665-670 (2003)

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