Role of the Fas/Fas ligand death receptor pathway in ginseng saponin metabolite-induced apoptosis in HepG2 cells
Role of the Fas/Fas ligand death receptor pathway in ginseng saponin metabolite-induced apoptosis in HepG2 cells
复制标题
DOI：
10.1007/bf02980081
复制
发表时间：
2004-04-01
影响因子：
6.7
通讯作者：
Lee, BH
中科院分区：
文献类型：
--
作者：
Oh, SH;Yin, HQ;Lee, BH
该研究小组在之前的研究中发现，人参皂苷代谢产物IH901通过线粒体介导的途径诱导HepG2细胞凋亡，导致caspase-9激活，进而激活caspase-3和caspase-8。在此基础上，研究了Fas/Fas配体(FasL)死亡受体通路在IH901诱导的HepG2细胞凋亡中的作用。IH901对Fas和Fas配体(FasL)的表达水平无明显影响，但在作用后18h显著降低。免疫沉淀法检测到IH901处理的HepG2细胞培养上清液中有可溶性FasL(SFasL)表达。SFasL水平升高与FasL水平呈负相关。用拮抗性抗Fas抗体预先孵育的HepG2细胞对IH901诱导的细胞死亡没有明显的保护作用。当IH901浓度为30um(24、48h)和40um(24h)时，IH901的细胞毒作用小于50%，抗Fas抗体可阻止IH901诱导的细胞死亡。然而，当IH901浓度为60um(24和48h)和40um(48h)时，细胞死亡率约为80%或更高，IH901的大部分化学预防和化疗作用都表现出来。阻断Fas受体不影响IH901诱导的细胞死亡。这些结果表明，Fas/FasL系统被激活，但不是IH901诱导细胞死亡所必需的，在药理上具有显著的浓度。
This research team found in previous studies, that the ginseng saponin metabolite IH901 induces apoptosis in HepG2 cells via a mitochondrial-mediated pathway, which resulted in the activation of caspase-9 and subsequently of caspase-3 and -8. Based on these results, the involvement of the Fas/Fas ligand (FasL) death-receptor pathway, in IH901-induced apoptosis in HepG2 cells, was investigated. Levels of Fas and the Fas ligand (FasL) mRNA or protein were not increased by IH901, rather they were decreased significantly at 18 h post treatment. Soluble FasL (sFasL) was detectable by immunoprecipitation analysis in the medium of HepG2 cells treated with IH901. Increased levels of sFasL were inversely correlated with the levels of FasL. Preincubation of HepG2 cells with antagonistic anti-Fas antibody showed little protective effect, if any, on IH901-induced cell death. At a 30 muM (24 and 48 h) and 40 muM (24 h) concentration of IH901, the cytotoxic effect of IH901 was less then 50%, anti-Fas antibody prevented IH901-induced cell death. However, at a 60 muM (24 and 48 h) and 40 muM (48 h) concentration of IH901, cell death rates were about 80% or more and most of the chemopreventive and chemotherapeutic effects of IH901 were manifested. Blocking the Fas receptor did not influence IH901-induced cell death. These results indicate that the Fas/FasL system is engaged, but not required for IH901-induced cell death, at pharmacologically significant concentrations.