Delneste Y, Jeannin P, Sebille E, Aubry J P, Bonnefoy J Y
Immunology Department, Geneva Biomedical Research Institute, Switzerland.
Eur J Immunol. 1996 Dec;26(12):2981-8. doi: 10.1002/eji.1830261225.
Thiol antioxidants have been shown to protect cells against apoptosis. Based on the role of Fas in T cell apoptosis, we investigated the effect of thiols on Fas expression. We report that the thiol N-acetyl-L-cysteine (NAC) prevents the induction of Fas on human peripheral blood T cells in a dose-dependent manner. It also down-regulates in a time- and dose-dependent manner Fas expression on Fas-expressing T cells. Although these effects were not mediated through de novo glutathione synthesis, only compounds with a free thiol group decreased membrane Fas expression. The decrease of Fas expression induced by NAC was not associated with a modulation of Fas mRNA transcription nor with an internalization, suggesting that NAC may affect the processing of Fas. Indeed, a soluble immunoreactive form of Fas was detected by ELISA and by Western blotting in the supernatants of Fas-expressing T cells treated with NAC. As a functional consequence, NAC partly protected Jurkat cells against Fas-mediated apoptotic cell death. Thus, this study shows that, by regulating Fas expression, the cytoprotective properties of NAC can be extended to Fas-mediated cell death.
硫醇抗氧化剂已被证明能保护细胞免受凋亡。基于Fas在T细胞凋亡中的作用，我们研究了硫醇对Fas表达的影响。我们报告硫醇N-乙酰-L-半胱氨酸（NAC）以剂量依赖的方式阻止人外周血T细胞上Fas的诱导。它还以时间和剂量依赖的方式下调表达Fas的T细胞上的Fas表达。尽管这些作用不是通过从头合成谷胱甘肽介导的，但只有具有游离硫醇基团的化合物会降低膜Fas表达。NAC诱导的Fas表达降低与Fas mRNA转录的调节或内化无关，这表明NAC可能影响Fas的加工。事实上，通过ELISA和蛋白质印迹法在经NAC处理的表达Fas的T细胞的上清液中检测到了可溶性免疫反应性Fas形式。作为功能结果，NAC部分保护Jurkat细胞免受Fas介导的凋亡性细胞死亡。因此，本研究表明，通过调节Fas表达，NAC的细胞保护特性可以扩展到Fas介导的细胞死亡。
