LoGerfo Annalisa, Chico Lucia, Borgia Loredana, Petrozzi Lucia, Rocchi Anna, D'Amelio Antonia, Carlesi Cecilia, Caldarazzo Ienco Elena, Mancuso Michelangelo, Siciliano Gabriele
Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
Department of Clinical and Experimental Medicine, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
Oxid Med Cell Longev. 2014;2014:432626. doi: 10.1155/2014/432626. Epub 2014 Feb 9.
Oxidative stress involvement has been strongly hypothesized among the possible pathogenic mechanisms of motor neuron degeneration in amyotrophic lateral sclerosis (ALS). The intracellular redox balance is finely modulated by numerous complex mechanisms critical for cellular functions, among which the nuclear factor erythroid-derived 2-like 2 (NFE2L2/Nrf2) pathways. We genotyped, in a cohort of ALS patients (n = 145) and healthy controls (n = 168), three SNPs in Nrf2 gene promoter: -653 A/G, -651 G/A, and -617 C/A and evaluated, in a subset (n = 73) of patients, advanced oxidation protein products (AOPP), iron-reducing ability of plasma (FRAP), and plasma thiols (-SH) as oxidative damage peripheral biomarkers. Nrf2 polymorphisms were not different among patients and controls. Increased levels of AOPP (P < 0.05) and decreased levels of FRAP (P < 0.001) have been observed in ALS patients compared with controls, but no difference in -SH values was found. Furthermore, no association was found between biochemical markers of redox balance and Nrf2 polymorphisms. These data confirm an altered redox balance in ALS and indicate that, while being abnormally modified compared to controls, the oxidative stress biomarkers assessed in this study are independent from the -653 A/G, -651 G/A, and -617 C/A Nrf2 SNPs in ALS patients.
氧化应激参与已被强烈假设为肌萎缩侧索硬化症（ALS）运动神经元变性可能的致病机制之一。细胞内氧化还原平衡由许多对细胞功能至关重要的复杂机制精细调节，其中包括核因子红细胞衍生2样2（NFE2L2/Nrf2）途径。我们对一组ALS患者（n = 145）和健康对照者（n = 168）的Nrf2基因启动子中的三个单核苷酸多态性（SNP）进行了基因分型：-653 A/G、-651 G/A和-617 C/A，并在一部分患者（n = 73）中评估了晚期氧化蛋白产物（AOPP）、血浆铁还原能力（FRAP）和血浆硫醇（-SH）作为氧化损伤外周生物标志物。患者和对照者之间的Nrf2多态性没有差异。与对照者相比，在ALS患者中观察到AOPP水平升高（P < 0.05）和FRAP水平降低（P < 0.001），但未发现-SH值有差异。此外，在氧化还原平衡的生化标志物与Nrf2多态性之间未发现关联。这些数据证实了ALS中氧化还原平衡的改变，并表明，虽然与对照者相比存在异常改变，但本研究中评估的氧化应激生物标志物与ALS患者中的-653 A/G、-651 G/A和-617 C/A Nrf2单核苷酸多态性无关。
