Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Cell Biochem Funct. 2024 Jun;42(4):e4025. doi: 10.1002/cbf.4025.
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease. Metabolic and mitochondrial dysregulation are critical causal factors in the pathogenesis and progression of RA. Mitochondrial dysfunction include abnormal energy metabolism, and excessive production of reactive oxygen species (ROS). This study aimed to investigate the adenosine triphosphate (ATP), mitochondrial membrane potential (ΔΨm), ROS, and mRNA expression level of ROMO1 (as ROS modulator) and OMA1 (as regulator mitochondrial dynamics) of peripheral blood mononuclear cells (PBMC) in RA patients. The study participants were 50 patients with RA and 50 sex- and age-matched healthy volunteers. PBMC of all participant were isolated by Ficoll-Paque. Alteration in ΔΨm and cellular ROS were measured using flow cytometry, ATP level was also assessed via luminometry, and ROMO1 and OMA1 mRNA expression via qRT-PCR assay. A significant decrease in ATP (p = .005) and ΔΨm (p < .001) was observed in the PBMC of RA compared to control. The ROS levels were significantly higher in the PBMC of RA compared to the control (p < .001). ROMO1 and OMA1 mRNA expression was also significantly increased in RA patients compared to control (p < .001). The decrease in ATP is strongly associated with ROS increasing in PBMC of RA patients, denoting an inverse and negative relationship between ATP and ROS production. Also, a decrease in ΔΨm was observed. It seems that in line with mitochondrial dysfunction in PBMC, increased expression of ROMO1 and OMA1 genes could also be involved in the development of RA.
类风湿关节炎（RA）是一种慢性炎症性自身免疫性疾病。代谢和线粒体失调是 RA 发病机制和进展的关键致病因素。线粒体功能障碍包括异常能量代谢和活性氧（ROS）的过度产生。本研究旨在探讨 RA 患者外周血单个核细胞（PBMC）中的三磷酸腺苷（ATP）、线粒体膜电位（ΔΨm）、ROS 以及 ROMO1（作为 ROS 调节剂）和 OMA1（作为调节线粒体动力学的调节剂）的 mRNA 表达水平。研究对象为 50 例 RA 患者和 50 名性别和年龄匹配的健康志愿者。所有参与者的 PBMC 均采用 Ficoll-Paque 分离。通过流式细胞术测量 ΔΨm 和细胞内 ROS 的变化，通过发光法评估 ATP 水平，通过 qRT-PCR 测定 ROMO1 和 OMA1 mRNA 表达。与对照组相比，RA 患者的 PBMC 中 ATP（p=0.005）和 ΔΨm（p<0.001）显著降低。RA 患者的 PBMC 中 ROS 水平明显高于对照组（p<0.001）。与对照组相比，RA 患者的 ROMO1 和 OMA1 mRNA 表达也显著增加（p<0.001）。RA 患者 PBMC 中 ATP 的减少与 ROS 的增加密切相关，表明 ATP 和 ROS 产生之间存在反比负相关关系。此外，还观察到 ΔΨm 的下降。似乎与 PBMC 中线粒体功能障碍一致，ROMO1 和 OMA1 基因的表达增加也可能参与 RA 的发生。
