Scientific Research Management Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, China.
Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, China.
Biochem Biophys Res Commun. 2019 Oct 20;518(3):451-458. doi: 10.1016/j.bbrc.2019.08.041. Epub 2019 Aug 28.
Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra pars compacta (SNpc). Tripartite motif 10 (TRIM10) belongs to the TRIM family of proteins and has been implicated to play a role in in PD, although supporting evidence has yet to be established. 1-methyl-4-phenylpyridinium (MPP+), the metabolite of MPTP (Mitochondrial parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine), is often used to generate a cellular model of PD. In this study, we found that MPP + inhibited cell proliferation and induced TRIM10 expression. Knockdown of TRIM10 alleviated cell apoptosis and ROS generation induced by MPP+. Further, MPP + decreased the expression of dual specificity phosphatase 6 (DUSP6) and this effect was reversed by TRIM10 knockdown. Moreover, DUSP6 alleviated cell apoptosis and ROS generation induced by TRIM10. Of note, TRIM10 suppressed DUSP6 by promoting DUSP6 ubiquitination. In conclusion, silencing of TRIM10 reduced cell apoptosis and ROS levels in a cellular model of PD, suggesting a potential role of TRIM10 in PD treatment.
帕金森病(PD)是第二常见的神经退行性疾病,其特征是黑质致密部(SNpc)多巴胺能神经元丧失、炎症和氧化应激损伤。三基序蛋白 10(TRIM10)属于 TRIM 蛋白家族,据报道在 PD 中发挥作用,但尚未建立支持证据。1-甲基-4-苯基吡啶(MPP+)是 MPTP(Mitochondrial parkinsonian neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine)的代谢物,常被用于生成 PD 的细胞模型。在这项研究中,我们发现 MPP+抑制细胞增殖并诱导 TRIM10 表达。TRIM10 敲低减轻了 MPP+诱导的细胞凋亡和 ROS 生成。进一步研究表明,MPP+降低了双特异性磷酸酶 6(DUSP6)的表达,而 TRIM10 敲低逆转了这一效应。此外,DUSP6 减轻了 TRIM10 诱导的细胞凋亡和 ROS 生成。值得注意的是,TRIM10 通过促进 DUSP6 泛素化来抑制 DUSP6。综上所述,沉默 TRIM10 可减少 PD 细胞模型中的细胞凋亡和 ROS 水平,提示 TRIM10 在 PD 治疗中的潜在作用。