The Effects of Ascorbate, N-Acetylcysteine, and Resveratrol on Fibroblasts from Patients with Mitochondrial Disorders.
The Effects of Ascorbate, N-Acetylcysteine, and Resveratrol on Fibroblasts from Patients with Mitochondrial Disorders.
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DOI：
10.3390/jcm6010001
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发表时间：
2016-12-22
影响因子：
3.9
通讯作者：
Saada A
中科院分区：
文献类型：
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作者：
Douiev L;Soiferman D;Alban C;Saada A
活性氧（ROS）被认为与影响氧化磷酸化的先天性线粒体疾病（OXPHOS）的发病机制有关。在目前的研究中，我们的特点是三个小分子的抗氧化性能（N-乙酰半胱氨酸，抗坏血酸，白藜芦醇）对ROS的生产和几个OXPHOS参数（生长在无葡萄糖培养基中，ATP生产，线粒体含量和膜电位（MMP））的影响，在原代成纤维细胞来自7个不同的分子定义和未定义的线粒体疾病。N-乙酰半胱氨酸似乎是最有益的化合物，可以减少活性氧，同时增加一些患者细胞的生长和ATP产生。抗坏血酸对ROS、ATP产生和线粒体含量表现出可变的积极或消极影响，而与白藜芦醇一起孵育对某些细胞中的ATP产生和MMP没有影响或有不利影响。个体反应强调了在评估线粒体疾病的抗氧化剂治疗选择时，除了ROS之外还研究多个参数以获得对OXPHOS的总体影响的更平衡观点的重要性。
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 (N-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. N-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.