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硒转录组学分析在帕金森病小鼠模型的脑区中鉴定出标志性硒蛋白。

Selenotranscriptomic Analyses Identify Signature Selenoproteins in Brain Regions in a Mouse Model of Parkinson's Disease.

作者信息

Zhang Xiong, Ye Yang-Lie, Zhu Hui, Sun Sheng-Nan, Zheng Jing, Fan Hui-Hui, Wu Hong-Mei, Chen Song-Fang, Cheng Wen-Hsing, Zhu Jian-Hong

机构信息

Department of Neurology, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.

Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

PLoS One. 2016 Sep 22;11(9):e0163372. doi: 10.1371/journal.pone.0163372. eCollection 2016.

Abstract

Genes of selenoproteome have been increasingly implicated in various aspects of neurobiology and neurological disorders, but remain largely elusive in Parkinson's disease (PD). In this study, we investigated the selenotranscriptome (24 selenoproteins in total) in five brain regions (cerebellum, substantia nigra, cortex, pons and hippocampus) by real time qPCR in a two-phase manner using a mouse model of chronic PD. A wide range of changes in selenotranscriptome was observed in a manner depending on selenoproteins and brain regions. While Selv mRNA was not detectable and Dio1& 3 mRNA levels were not affected, 1, 11 and 9 selenoproteins displayed patterns of increase only, decrease only, and mixed response, respectively, in these brain regions of PD mice. In particular, the mRNA expression of Gpx1-4 showed only a decreased trend in the PD mouse brains. In substantia nigra, levels of 17 selenoprotein mRNAs were significantly decreased whereas no selenoprotein was up-regulated in the PD mice. In contrast, the majority of selenotranscriptome did not change and a few selenoprotein mRNAs that respond displayed a mixed pattern of up- and down-regulation in cerebellum, cortex, hippocampus, and/or pons of the PD mice. Gpx4, Sep15, Selm, Sepw1, and Sepp1 mRNAs were most abundant across all these five brain regions. Our results showed differential responses of selenoproteins in various brain regions of the PD mouse model, providing critical selenotranscriptomic profiling for future functional investigation of individual selenoprotein in PD etiology.

摘要

硒蛋白组的基因在神经生物学和神经系统疾病的各个方面的作用日益受到关注,但在帕金森病(PD)中仍 largely 难以捉摸。在本研究中,我们使用慢性 PD 小鼠模型,通过实时定量 PCR 分两个阶段研究了五个脑区(小脑、黑质、皮层、脑桥和海马体)中的硒转录组(共 24 种硒蛋白)。观察到硒转录组存在广泛变化,其方式取决于硒蛋白和脑区。虽然未检测到 Selv mRNA,且 Dio1 和 3 mRNA 水平未受影响,但在 PD 小鼠的这些脑区中,分别有 1 种、11 种和 9 种硒蛋白呈现仅增加、仅减少和混合反应的模式。特别是,Gpx1 - 4 的 mRNA 表达在 PD 小鼠脑中仅呈下降趋势。在黑质中,17 种硒蛋白 mRNA 的水平显著降低,而在 PD 小鼠中没有硒蛋白上调。相比之下,在 PD 小鼠的小脑、皮层、海马体和/或脑桥中,大多数硒转录组没有变化,少数有反应的硒蛋白 mRNA 呈现上调和下调的混合模式。Gpx4、Sep15、Selm、Sepw1 和 Sepp1 mRNA 在所有这五个脑区中最为丰富。我们的结果显示了 PD 小鼠模型不同脑区中硒蛋白的差异反应,为未来对 PD 病因中单个硒蛋白的功能研究提供了关键的硒转录组学图谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f07b/5033372/d0bdea435382/pone.0163372.g001.jpg

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