Department of Neurology, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China.
Department of Neurology, The First People's Hospital of Huaihua City, Hunan 418000, China.
Biomed Res Int. 2020 Sep 21;2020:4658109. doi: 10.1155/2020/4658109. eCollection 2020.
Parkinson's disease (PD) is the second most common neurodegenerative disease in middle-aged and elderly people. However, the etiology and pathogenesis of PD are still unclear and there is a lack of reliable biomarkers for early molecular diagnosis. Parkin (encoded by ) is a ubiquitin E3 ligase that participates in mitochondrial homeostasis, the ubiquitin-proteasome pathway, oxidative stress response, and cell death pathways, which are involved in the pathogenesis of PD. However, Parkin is also expressed in peripheral blood lymphocytes (PBLs). In this study, permanent lymphocyte lines were established from the peripheral blood of sporadic PD (sPD) patients, mutation carriers, and healthy controls. Reactive oxygen species (ROS), function of the mitochondrial respiratory chain complex I, and apoptosis were analyzed in the PBLs. There was no significant difference in ROS, mitochondrial respiratory chain complex I, and apoptosis between the experimental groups and the control group without paraquat treatment. Compared with the control group of healthy subjects, we found an increase of ROS (control 100 ± 0, sPD 275.53 ± 79.11, and C441R 340 ± 99.67) and apoptosis, as well as a decline in the function of mitochondrial respiratory chain complex I in PBLs of mutation carriers and sPD after the treatment of paraquat (control 0.65 ± 0.08, sPD 0.44 ± 0.08, and C441R 0.32 ± 0.08). Moreover, overexpression of the wild-type (WT) in HeLa cells and immortalized PBLs could rescue mitochondrial function and partially inhibit apoptosis following paraquat treatment, while the C441R mutation could not. Thus, ROS levels, activity of mitochondrial respiratory chain complex I, and apoptosis of PBLs are potential diagnostic biomarkers of PD.
帕金森病（PD）是中老年人中第二常见的神经退行性疾病。然而，PD 的病因和发病机制尚不清楚，缺乏可靠的早期分子诊断生物标志物。Parkin（由 编码）是一种泛素 E3 连接酶，参与线粒体稳态、泛素-蛋白酶体途径、氧化应激反应和细胞死亡途径，这些途径都与 PD 的发病机制有关。然而，Parkin 也在外周血淋巴细胞（PBLs）中表达。在这项研究中，从散发性 PD（sPD）患者、 突变携带者和健康对照者的外周血中建立了永久性淋巴细胞系。分析了 PBLs 中的活性氧（ROS）、线粒体呼吸链复合物 I 的功能和细胞凋亡。未经百草枯处理时，实验组与对照组之间 ROS、线粒体呼吸链复合物 I 和细胞凋亡无显著差异。与健康对照组相比，我们发现突变携带者和 sPD 的 PBLs 在百草枯处理后 ROS（对照组 100±0，sPD 275.53±79.11，C441R 340±99.67）增加和细胞凋亡增加，以及线粒体呼吸链复合物 I 的功能下降（对照组 0.65±0.08，sPD 0.44±0.08，C441R 0.32±0.08）。此外，在 HeLa 细胞和永生化 PBLs 中过表达野生型（WT） 可以挽救百草枯处理后的线粒体功能并部分抑制细胞凋亡，而 C441R 突变则不能。因此，PBLs 的 ROS 水平、线粒体呼吸链复合物 I 的活性和细胞凋亡可能是 PD 的潜在诊断生物标志物。
