Department of Biological and Environmental Sciences and Technologies, University of Salento, via Monteroni, Lecce, Italy.
Laboratory of Clinical Proteomic, "Giovanni Paolo II" Hospital, ASL-Lecce, Piazzetta F. Muratore, Lecce, Italy.
Biochim Biophys Acta Mol Basis Dis. 2018 May;1864(5 Pt A):1828-1838. doi: 10.1016/j.bbadis.2018.03.007. Epub 2018 Mar 8.
Although many studies have been carried out in order to understand the implication of copper (Cu) in the pathogenesis of multiple sclerosis (MS), the exact role that this metal plays in the disease is not still clear. Because of the lack of information in this subject, the present study compared the serum and cerebrospinal (CSF) levels of copper in MS patients in respect to a control group, matched for age and sex, finding a significant increase of metal concentrations, in both biological fluids of MS subjects. To confirm the possible impairment of Cu metabolism, we analyzed ceruloplasmin (Cp) level and activity, seeing as this protein is an established peripheral marker in diseases associated with Cu imbalance. By comparing these two parameters between control and MS subjects, we found an increase of Cp levels, associated with a decrease in Cp activity, in the second group. By analysing these data, free copper levels were calculated, significantly increased in serum of MS subjects; the increase in free copper could be one of the predisposing factors responsible for the Cu altered levels in CSF of MS patients. At the same time, this alteration could be attributable to the inability to incorporate Cu by Cp, probably due to the high oxidative environment found in serum of MS patients. Overall, all these copper alterations may play a role in MS pathogenesis.
尽管已经进行了许多研究来了解铜 (Cu) 在多发性硬化症 (MS) 发病机制中的意义，但这种金属在疾病中的确切作用仍不清楚。由于该主题缺乏信息，本研究比较了 MS 患者的血清和脑脊液 (CSF) 中铜的水平与年龄和性别相匹配的对照组，发现两种生物体液中金属浓度均显著升高。为了确认 Cu 代谢可能受损，我们分析了铜蓝蛋白 (Cp) 的水平和活性，因为该蛋白是与 Cu 失衡相关疾病的既定外周标志物。通过比较对照组和 MS 组这两个参数，我们发现第二组 Cp 水平升高，同时 Cp 活性降低。通过分析这些数据，计算出血清中游离铜水平显著升高;游离铜的增加可能是导致 MS 患者 CSF 中 Cu 水平改变的一个促成因素。同时，这种改变可能归因于 Cp 无法结合 Cu，这可能是由于 MS 患者血清中存在高氧化环境所致。总的来说，所有这些铜的改变都可能在 MS 的发病机制中起作用。
