School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
Mediators Inflamm. 2013;2013:953462. doi: 10.1155/2013/953462. Epub 2013 Apr 3.
Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia and progressive joint destruction. The impaired apoptosis of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) is pivotal in this process. However, the molecular mechanisms responsible for the reduced apoptosis are not fully understood. Both nitric oxide and thioredoxin 1 as two important mediators are widely investigated in the pathogenesis of rheumatoid arthritis. Interestingly, studies have showed that thioredoxin 1 may serve as a master regulator of S-nitrosylation of caspase-3 to fine-tune apoptosis in vivo. Thus, it is anticipated that further investigations on the role of thioredoxin 1 in the S-nitrosylation and denitrosylation of caspase-3 in RA-FLS will likely provide a novel understanding of mechanisms implicated in the impaired apoptosis of RA-FLS. In this paper, we will provide an overview on pathways involved in the reduced apoptosis of RA-FLS and then discuss specially the possible roles of nitric oxide and the thioredoxin 1 redox system associated with apoptosis of RA-FLS.
类风湿关节炎是一种慢性炎症性疾病，其特征为滑膜增生和进行性关节破坏。类风湿关节炎成纤维样滑膜细胞（RA-FLS）凋亡受损在这一过程中起着关键作用。然而，导致凋亡减少的分子机制尚不完全清楚。一氧化氮和硫氧还蛋白 1 作为两种重要的介质，在类风湿关节炎的发病机制中得到了广泛的研究。有趣的是，研究表明，硫氧还蛋白 1 可能作为 caspase-3 的 S-亚硝基化的主调控因子，以精细调节体内的凋亡。因此，预计进一步研究硫氧还蛋白 1 在 RA-FLS 中 caspase-3 的 S-亚硝基化和去亚硝基化中的作用，可能为理解 RA-FLS 凋亡受损的机制提供新的认识。本文将概述 RA-FLS 凋亡减少的相关途径，然后特别讨论一氧化氮和与 RA-FLS 凋亡相关的硫氧还蛋白 1 氧化还原系统的可能作用。
