完整外周血单核细胞中的线粒体呼吸与运动障碍患者中的 Sirtuin 3 活性。
Mitochondrial Respiration in Intact Peripheral Blood Mononuclear Cells and Sirtuin 3 Activity in Patients with Movement Disorders.
机构信息
Department of Neurochemistry and Neuropathology, Poznan University of Medical Sciences, Przybyszewskiego str. 49, 60-355 Poznan, Poland.
Department of Neurology, Poznan University of Medical Sciences, Przybyszewskiego str. 49, 60-355 Poznan, Poland.
出版信息
Oxid Med Cell Longev. 2017;2017:9703574. doi: 10.1155/2017/9703574. Epub 2017 Sep 10.
OBJECTIVE
Mitochondrial dysfunction is considered a unifying pathophysiological explanation for movement disorders. Sirtuin 3 (SIRT3) exhibits deacetylase activity and antioxidant properties. The aim of the study was to analyze the mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) and the SIRT3 activity in patients with movement disorders.
METHODS
Mitochondrial respiration was analyzed in intact PBMCs using the ROUTINE, LEAK, electron transfer system (ETS), and residual oxygen consumption (ROX) protocol by means of high-resolution respirometry. The SIRT3 expression and PBMC activity were measured using fluorometry. Ultrasound measurements of the echogenicity of the substantia nigra and the diameter of the 3rd ventricle were also performed.
RESULTS
Patients with movement disorders exhibited a lower ROUTINE respiration than controls ( = 0.0237). Reduced oxygen fluxes in the LEAK ( = 0.033) and ROX ( = 0.0486) states were observed in patients with movement disorders compared with controls. Decreased ROUTINE respiration ( = 0.007) and oxygen flux in the LEAK state ( = 0.0203) were observed in patients with PD with substantia nigra hyperechogenicity compared with controls. Decreased SIRT 3 deacetylase activity was found in patients with movement disorders.
CONCLUSION
Impaired mitochondrial respiration in intact PBMCs was associated with inhibited SIRT3 activity and neurodegeneration measures evaluated using ultrasound in patients with PD.
目的
线粒体功能障碍被认为是运动障碍的一种统一的病理生理学解释。Sirtuin 3（SIRT3）具有去乙酰化酶活性和抗氧化特性。本研究旨在分析运动障碍患者外周血单个核细胞（PBMC）中的线粒体呼吸和 SIRT3 活性。
方法
使用高分辨率呼吸计通过 ROUTINE、LEAK、电子传递系统（ETS）和剩余耗氧量（ROX）方案分析完整 PBMC 中的线粒体呼吸。使用荧光法测量 SIRT3 表达和 PBMC 活性。还对黑质的回声强度和第三脑室直径进行了超声测量。
结果
运动障碍患者的 ROUTINE 呼吸比对照组低（=0.0237）。与对照组相比，运动障碍患者的 LEAK（=0.033）和 ROX（=0.0486）状态下的氧气通量减少。与对照组相比，黑质回声增强的 PD 患者的 ROUTINE 呼吸（=0.007）和 LEAK 状态下的氧气通量（=0.0203）减少。运动障碍患者的 SIRT3 去乙酰化酶活性降低。
结论
完整 PBMC 中的线粒体呼吸受损与 SIRT3 活性抑制以及使用超声评估的 PD 患者的神经退行性变指标有关。
Zotero 插件