Douiev Liza, Soiferman Devorah, Alban Corinne, Saada Ann
Monique and Jacques Roboh Department of Genetic Research and the Department of Genetic and Metabolic Diseases, Hadassah-Hebrew University Hospital, 91120 Jerusalem, Israel.
J Clin Med. 2016 Dec 22;6(1):1. doi: 10.3390/jcm6010001.
Reactive oxygen species (ROS) are assumed to be implicated in the pathogenesis of inborn mitochondrial diseases affecting oxidative phosphorylation (OXPHOS). In the current study, we characterized the effects of three small molecules with antioxidant properties (-acetylcysteine, ascorbate, and resveratrol) on ROS production and several OXPHOS parameters (growth in glucose free medium, ATP production, mitochondrial content and membrane potential (MMP)), in primary fibroblasts derived from seven patients with different molecularly defined and undefined mitochondrial diseases. -acetylcysteine appeared to be the most beneficial compound, reducing ROS while increasing growth and ATP production in some patients' cells. Ascorbate showed a variable positive or negative effect on ROS, ATP production, and mitochondrial content, while incubation with resveratrol disclosed either no effect or detrimental effect on ATP production and MMP in some cells. The individual responses highlight the importance of investigating multiple parameters in addition to ROS to obtain a more balanced view of the overall effect on OXPHOS when evaluating antioxidant treatment options for mitochondrial diseases.
活性氧（ROS）被认为与影响氧化磷酸化（OXPHOS）的先天性线粒体疾病的发病机制有关。在本研究中，我们表征了三种具有抗氧化特性的小分子（N-乙酰半胱氨酸、抗坏血酸和白藜芦醇）对来自七名患有不同分子定义和未定义线粒体疾病患者的原代成纤维细胞中ROS产生以及几个OXPHOS参数（在无葡萄糖培养基中的生长、ATP产生、线粒体含量和膜电位（MMP））的影响。N-乙酰半胱氨酸似乎是最有益的化合物，在一些患者的细胞中可减少ROS，同时增加生长和ATP产生。抗坏血酸对ROS、ATP产生和线粒体含量表现出可变的正向或负向作用，而用白藜芦醇孵育在一些细胞中对ATP产生和MMP要么无影响，要么有有害影响。个体反应突出了在评估线粒体疾病的抗氧化治疗方案时，除了ROS之外还研究多个参数以更全面地了解对OXPHOS总体影响的重要性。
