Hargreaves Iain, Mody Nimesh, Land John, Heales Simon
WC1N 3BG, UK.
L3 5UA, UK.
J Clin Med. 2018 Feb 20;7(2):36. doi: 10.3390/jcm7020036.
Evidence of mitochondrial respiratory chain (MRC) dysfunction and oxidative stress has been implicated in the pathophysiology of multiple sclerosis (MS). However, at present, there is no reliable low invasive surrogate available to evaluate mitochondrial function in these patients. In view of the particular sensitivity of MRC complex IV to oxidative stress, the aim of this study was to assess blood mononuclear cell (BMNC) MRC complex IV activity in MS patients and compare these results to age matched controls and MS patients on β-interferon treatment.
Spectrophotometric enzyme assay was employed to measure MRC complex IV activity in blood mononuclear cell obtained multiple sclerosis patients and aged matched controls.
MRC Complex IV activity was found to be significantly decreased ( < 0.05) in MS patients (2.1 ± 0.8 k/nmol × 10; mean ± SD] when compared to the controls (7.2 ± 2.3 k/nmol × 10). Complex IV activity in MS patients on β-interferon (4.9 ± 1.5 k/nmol × 10) was not found to be significantly different from that of the controls.
This study has indicated evidence of peripheral MRC complex IV deficiency in MS patients and has highlighted the potential utility of BMNCs as a potential means to evaluate mitochondrial function in this disorder. Furthermore, the reported improvement of complex IV activity may provide novel insights into the mode(s) of action of β-interferon.
线粒体呼吸链(MRC)功能障碍和氧化应激的证据已被认为与多发性硬化症(MS)的病理生理学有关。然而,目前尚无可靠的低侵入性替代指标可用于评估这些患者的线粒体功能。鉴于MRC复合体IV对氧化应激具有特殊敏感性,本研究旨在评估MS患者血液单核细胞(BMNC)中MRC复合体IV的活性,并将这些结果与年龄匹配的对照组以及接受β-干扰素治疗的MS患者进行比较。
采用分光光度酶法测定多发性硬化症患者和年龄匹配的对照组血液单核细胞中MRC复合体IV的活性。
与对照组(7.2±2.3k/nmol×10)相比,MS患者(2.1±0.8k/nmol×10;平均值±标准差)的MRC复合体IV活性显著降低(<0.05)。接受β-干扰素治疗的MS患者的复合体IV活性(4.9±1.5k/nmol×10)与对照组无显著差异。
本研究表明MS患者存在外周MRC复合体IV缺乏的证据,并突出了BMNC作为评估该疾病线粒体功能潜在手段的潜在效用。此外,所报道的复合体IV活性的改善可能为β-干扰素的作用方式提供新的见解。