الملخص
Objective @#To investigate the expression of genes and proteins in the peripheral blood mononuclear cell ( PBMC) cystine / glutamate antiporter system (System Xc-) / glutathione ( GSH) / glutathione peroxidase 4 ( GPX4) ferroptosis pathway and its influence on inflammatory factors in patients with rheumatoid arthritis ( RA) ．@*Methods @#30 patients with RA and 30 healthy participants were enrolled．PBMCs were isolated using Ficoll-hypaque density gradient centrifugation．The cells were categorized into the healthy control，RA，ferroptosis inhibitor，ferroptosis in- ducer group．The cell viability was checked using the cell counting kit-8 ( CCK-8) method．Intracellular Fe2 + rela- tive fluorescence intensity and reactive oxygen species (ROS) levels were detected using the FerroOrange and Di- hydroethidium (DHE) fluorescent probes，respectively．Western blot and real-time quantitative PCR (qPCR) de- tected the expression of nuclear factor erythroid 2-related factor 2 ( Nrf2 ) ，solute carrier family 7 member 11 (SLC7A11) ，GPX4 proteins and mRNA．And the flow cytometry quantified the levels of tumor necrosis factor α (TNF-α) ，Interleukin (IL) -1，and IL-6 in the supernatant of each cell group. @*Results @# Compared to the healthy control group，the RA group showed a significantly increased Fe2 + concentration and elevated ROS levels，reduced expression of Nrf2，SLC7A11 and GPX4 proteins and mRNA，and increased contents of TNF-α , IL-1 and IL-6 in PBMC supernatant，and the differences were statistically significant．The concentration of Fe2 + and ROS levels in the inhibitor group were lower than those in the RA group，the proteins expressions of Nrf2，SLC7A11 and GPX4 increased，the mRNA expressions of SLC7A11 and GPX4 increased，the content of IL-6 in the PBMC supernatant decreased but the content of TNF-α increased，and the differences were statistically significant．In contrast，the in- ducer group，when compared to the RA group，displayed increased ROS levels，reduced expression of SLC7A11 protein and mRNA and decreased expression of Nrf2 protein，and the contents of TNF-α and IL-1 in the PBMC su- pernatant increased，but the expression of GPX4 protein increased ，and the differences were statistically signifi- cant．The inducer group，compared to the RA group，showed increased cell viability，and the difference was statis- tically significant (P＜0. 000 1) ．@*Conclusion @# The presence of ferroptosis in PBMC in RA patients，inhibiting or inducing PBMC ferroptosis in RA patients，will inhibit or promote the secretion of inflammatory factors．Inhibition of PBMC ferroptosis in RA patients may be helpful in the treatment of RA.
الملخص
Ferroptosis is an iron-dependent cell death caused by phospholipid peroxidation damage of polyunsaturated fatty acids on cell membranes and involves several pathways, including the iron homeostasis regulatory pathway, the cystine glutamate reverse transporter (system Xc) pathway and the voltage-dependent anion channel (VDAC) pathway. Ferroptosis is involved in the development of several diseases (e. g. myocardial infarction, stroke, cancer and degenerative diseases). The ubiquitination is an important post-translational modification of various protein molecules in the organism. Studies have shown that regulating the ubiquitination of ferroptosis pathway-related molecules can control cellular ferroptosis. Targeting the ubiquitination of ferroptosis pathway-related molecules can effectively promote or inhibit ferroptosis, which is expected to be a new strategy for the treatment of cancer or cardiovascular diseases. In this paper we review the progress of the ferroptosis pathways and the ubiquitination modification of ferroptosis-related molecules.