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WT 和 Per1/Per2 小鼠的多组织生物钟蛋白质组图谱。

Multitissue Circadian Proteome Atlas of WT and Per1/Per2 Mice.

机构信息

Westlake Center for Intelligent Proteomics, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou, Zhejiang Province, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou, Zhejiang Province, China; Research Center for Industries of the Future, Westlake University, Hangzhou, Zhejiang, China.

Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda Genomic Resource Center, Soochow University, Suzhou, Jiangsu Province, China.

出版信息

Mol Cell Proteomics. 2023 Dec;22(12):100675. doi: 10.1016/j.mcpro.2023.100675. Epub 2023 Nov 7.

Abstract

The molecular basis of circadian rhythm, driven by core clock genes such as Per1/2, has been investigated on the transcriptome level, but not comprehensively on the proteome level. Here we quantified over 11,000 proteins expressed in eight types of tissues over 46 h with an interval of 2 h, using WT and Per1/Per2 double knockout mouse models. The multitissue circadian proteome landscape of WT mice shows tissue-specific patterns and reflects circadian anticipatory phenomena, which are less obvious on the transcript level. In most peripheral tissues of double knockout mice, reduced protein cyclers are identified when compared with those in WT mice. In addition, PER1/2 contributes to controlling the anticipation of the circadian rhythm, modulating tissue-specific cyclers as well as key pathways including nucleotide excision repair. Severe intertissue temporal dissonance of circadian proteome has been observed in the absence of Per1 and Per2. The γ-aminobutyric acid might modulate some of these temporally correlated cyclers in WT mice. Our study deepens our understanding of rhythmic proteins across multiple tissues and provides valuable insights into chronochemotherapy. The data are accessible at https://prot-rhythm.prottalks.com/.

摘要

昼夜节律的分子基础是由核心时钟基因(如 Per1/2)驱动的,已经在转录组水平上进行了研究,但在蛋白质组水平上尚未全面研究。在这里,我们使用 WT 和 Per1/Per2 双敲除小鼠模型,在 46 小时内每隔 2 小时定量分析了 8 种组织中超过 11000 种蛋白质的表达情况。WT 小鼠的多组织昼夜节律蛋白质组景观显示出组织特异性模式,并反映了昼夜节律预期现象,而在转录水平上这些现象不太明显。与 WT 小鼠相比,在双敲除小鼠的大多数外周组织中,减少了蛋白质循环。此外,PER1/2 有助于控制昼夜节律的预期,调节组织特异性循环以及包括核苷酸切除修复在内的关键途径。当没有 Per1 和 Per2 时,观察到昼夜节律蛋白质组在不同组织之间存在严重的时间不协调性。γ-氨基丁酸可能会调节 WT 小鼠中一些这些时间相关的循环蛋白。我们的研究加深了我们对多个组织中节律蛋白的理解,并为 chronochemotherapy 提供了有价值的见解。数据可在 https://prot-rhythm.prottalks.com/ 获取。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e5e4/10750102/bc9c31840d95/ga1.jpg

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