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在 MPTP 诱导的帕金森病小鼠的肌肉中,α-突触核蛋白的增加与减少相关。

Decrease Associated with Alpha-Synuclein Increase in Muscles of MPTP-Induced Parkinson's Disease Mice.

机构信息

Department of Meridian and Acupoint, College of Korean Medicine, Sang Ji University, Wonju 26339, Korea.

Research Institute of Korean Medicine, Sang Ji University, Wonju 26339, Korea.

出版信息

Int J Mol Sci. 2021 Aug 29;22(17):9375. doi: 10.3390/ijms22179375.

DOI:10.3390/ijms22179375
PMID:34502283
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8430752/
Abstract

Parkinson's disease (PD) is characterized by a loss of dopaminergic cells in the substantia nigra, and its histopathological features include the presence of fibrillar aggregates of α-synuclein (α-syn), which are called Lewy bodies and Lewy neurites. Lewy pathology has been identified not only in the brain but also in various tissues, including muscles. This study aimed to investigate the link between serine/arginine-rich protein specific kinase 3 () and α-syn in muscles in PD. We conducted experiments on the quadriceps femoris of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model and the C2C12 cell line after treatment with 1-methyl-4-phenylpyridinium (MPP+) and short interfering RNA (siRNA). Compared to the control group, the MPTP group showed significantly reduced expression of srpk3, but increased expression of α-syn. In MPP+-treated C2C12 cells, srpk3 expression gradually decreased and α-syn expression increased with the increasing MPP+ concentration. Moreover, experiments in C2C12 cells using srpk3 siRNA showed increased expressions of α-syn and phosphorylated α-syn. Our results showed that srpk3 expression could be altered by MPTP intoxication in muscles, and this change may be related to changes in α-syn expression. Furthermore, this study could contribute to advancement of research on the mechanism by which srpk3 plays a role in PD.

摘要

帕金森病(PD)的特征是黑质中多巴胺能细胞的丧失,其组织病理学特征包括存在α-突触核蛋白(α-syn)的纤维状聚集物,称为路易体和路易神经突。路易体病理学不仅在大脑中,而且在包括肌肉在内的各种组织中都已被确定。本研究旨在探讨 PD 肌肉中丝氨酸/精氨酸丰富蛋白激酶 3(srpk3)和α-syn 之间的联系。我们对 1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的 PD 小鼠模型的股四头肌和经 1-甲基-4-苯基吡啶(MPP+)和短发夹 RNA(siRNA)处理的 C2C12 细胞系进行了实验。与对照组相比,MPTP 组 srpk3 的表达明显降低,但α-syn 的表达增加。在 MPP+处理的 C2C12 细胞中,srpk3 的表达逐渐降低,α-syn 的表达随着 MPP+浓度的增加而增加。此外,在使用 srpk3 siRNA 的 C2C12 细胞实验中,α-syn 和磷酸化α-syn 的表达增加。我们的结果表明,MPTP 中毒可改变肌肉中的 srpk3 表达,这种变化可能与α-syn 表达的变化有关。此外,这项研究可能有助于推进 srpk3 在 PD 中发挥作用的机制研究。

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