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

我们检测了泛素-蛋白酶体途径对Fas和Fas相关基因表达的影响以及对Fas介导的细胞凋亡的增敏作用。此外，我们还探讨了Fas介导的细胞凋亡的临床意义，尤其是在急性冠脉综合征中。研究结果如下。实验研究：1)泛素-蛋白酶体途径参与了Fas介导的人血管平滑肌细胞(VSMCs)和内皮细胞(ECs)的凋亡易感性。也就是说，蛋白酶体活性的抑制导致表面Fas的上调，从而导致Fas介导的细胞凋亡的敏化。临床研究：1)急性冠脉综合征患者外周血中可溶性FasL和单核细胞膜FasL浓度均高于健康对照组和稳定型心绞痛患者。2)可溶性FasL浓度与膜FasL浓度之间无相关性，提示二者受不同的调控机制。在结论中。1)Fas诱导的VSMCs和ECs的凋亡，至少在体外是由泛素-蛋白酶体途径调控的。2)Fas-FasL信号转导可能与急性冠脉综合征的发病机制有关。

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.