De Rasmo Domenico, Ferretta Anna, Russo Silvia, Ruggieri Maddalena, Lasorella Piergiorgio, Paolicelli Damiano, Trojano Maria, Signorile Anna
CNR-Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies, 70126 Bari, Italy.
Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari "Aldo Moro", 70124 Bari, Italy.
Biomedicines. 2020 Apr 11;8(4):85. doi: 10.3390/biomedicines8040085.
Multiple sclerosis (MS) is an autoimmune disease in which activated lymphocytes affect the central nervous system. Increase of reactive oxygen species (ROS), impairment of mitochondria-mediated apoptosis and mitochondrial alterations have been reported in peripheral lymphocytes of MS patients. Mitochondria-mediated apoptosis is regulated by several mechanisms and proteins. Among others, optic atrophy 1 (OPA1) protein plays a key role in the regulating mitochondrial dynamics, cristae architecture and release of pro-apoptotic factors. Very interesting, mutations in OPA1 gene, have been associated with multiple sclerosis-like disorder. We have analyzed OPA1 and some factors involved in its regulation. Fifteen patients with MS and fifteen healthy control subjects (HC) were enrolled into the study and peripheral blood mononuclear cells (PBMCs) were isolated. HO level was measured spectrofluorimetrically, OPA1, PHB2, SIRT3, and OMA1 were analyzed by western blotting. Statistical analysis was performed using Student's -test. The results showed that PBMC of MS patients were characterized by a deregulation of OPA1 processing associated with increased HO production, inactivation of OMA1 and increase of PHB2 protein level. The presented data suggest that the alteration of PHB2, OMA1, and OPA1 processing could be involved in resistance towards apoptosis. These molecular parameters could also be useful to assess disease activity.
多发性硬化症（MS）是一种自身免疫性疾病，其中活化的淋巴细胞会影响中枢神经系统。据报道，MS患者外周淋巴细胞中活性氧（ROS）增加、线粒体介导的凋亡受损以及线粒体改变。线粒体介导的凋亡受多种机制和蛋白质调控。其中，视神经萎缩蛋白1（OPA1）在调节线粒体动力学、嵴结构和促凋亡因子释放方面起关键作用。非常有趣的是，OPA1基因突变与多发性硬化症样疾病有关。我们分析了OPA1及其一些调控因子。15例MS患者和15名健康对照者（HC）纳入研究，分离外周血单个核细胞（PBMC）。采用荧光分光光度法测定HO水平，通过蛋白质印迹法分析OPA1、PHB2、SIRT3和OMA1。使用学生t检验进行统计分析。结果表明，MS患者的PBMC具有OPA1加工失调的特征，这与HO产生增加、OMA1失活和PHB2蛋白水平升高有关。所呈现的数据表明，PHB2、OMA1和OPA1加工的改变可能与细胞凋亡抗性有关。这些分子参数也可能有助于评估疾病活动。
