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

我们研究了泛素-蛋白酶体途径对Fas或Fas相关mRNA的表达以及Fas介导的细胞凋亡的致敏性的影响。此外，我们研究了fas介导的细胞凋亡的临床意义，特别是在急性冠状动脉综合征中。结果如下：实验研究：1)在体外培养的人血管平滑肌细胞（VSMCs）和内皮细胞（ECs）中，泛素-蛋白酶体通路均参与fas介导的细胞凋亡易感性。也就是说，抑制蛋白酶体活性诱导的表面Fas的上调导致Fas介导的细胞凋亡的增敏。临床研究：1)急性冠脉综合征患者外周血可溶性FasL浓度和单核细胞膜FasL浓度均高于健康志愿者和稳定型心绞痛患者。2)可溶性FasL浓度与膜性FasL浓度无相关性，说明两者受不同机制的调控。在结论。1)至少在体外，fas介导的VSMCs和ECs凋亡均受泛素-蛋白酶体途径的调控。2) fasl - fasl信号转导可能与急性冠脉综合征的病理生理有关。

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.