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昼夜节律在大脑细胞蛋白质谱调控中的作用。

The role of circadian rhythm in the regulation of cellular protein profiles in the brain.

机构信息

Department of Physiology, School of Medicine, Istanbul Medipol University, İstanbul, Turkey.

Regenerative and Restorative Medicine Research Center (REMER), Research Institute for Health Sciences and Technologies (SABITA), Istanbul Medipol University, İstanbul, Turkey.

出版信息

Turk J Med Sci. 2021 Oct;51(5):2705-2715. doi: 10.3906/sag-2010-336. Epub 2021 Oct 21.

DOI:10.3906/sag-2010-336
PMID:33356029
Abstract

BACKGROUND

Circadian rhythm plays a significant role in the regulation of almost all kinds of physiological processes. In addition, it may also have a direct or indirect effect on the neurodegenerative processes, including Alzheimer's disease, Parkinson's disease, and ischemic stroke. Therefore, the identification of circadian rhythm-related proteins is crucial to be able to understand the molecular mechanism of the circadian rhythm and to define new therapeutic target for the treatment of degenerative disorders.

METHODS

To identify the light and dark regulated proteins, 8-12 weeks, male Balb/C mice were used at two different time points (morning (Zeitgeber time-0 (ZT0)) and midnight (ZT18)) under physiological conditions. Therefore, brain tissues were analyzed via liquid chromatography tandem mass spectrometry.

RESULTS

A total of 1621 different proteins were identified between ZT0 and ZT18 mice. Among these proteins, 23 proteins were differentially expressed (p < 0.05 and fold change 1.4) in ZT18 mice, 11 upregulated (AKAP10, ALDOC, BLK, NCALD, NFL, PDE10A, PICAL, PSMB6, RL10, SH3L3, and SYNJ1), and 12 downregulated (AT2A2, AT2B1, CPNE5, KAP3, MAON, NPM, PI51C, PPR1B, SAM50, TOM70, TY3H, and VAPA) as compared with ZT0 mice.

DISCUSSION

Taken together, here we identified circadian rhythm-related proteins, and our further analysis revealed that these proteins play significant roles in molecular function, membrane trafficking, biogenesis, cellular process, metabolic process, and neurodegenerative disorders such as Parkinson's disease.

摘要

背景

昼夜节律在几乎所有生理过程的调节中都起着重要作用。此外,它可能对神经退行性过程,包括阿尔茨海默病、帕金森病和缺血性中风,有直接或间接的影响。因此,识别与昼夜节律相关的蛋白质对于理解昼夜节律的分子机制以及为退行性疾病的治疗确定新的治疗靶点至关重要。

方法

为了鉴定光照和黑暗调节的蛋白质,在生理条件下,将 8-12 周龄雄性 Balb/C 小鼠在两个不同时间点(早上( Zeitgeber 时间 0(ZT0))和午夜(ZT18))进行处理。因此,通过液相色谱串联质谱法对脑组织进行分析。

结果

在 ZT0 和 ZT18 小鼠之间共鉴定出 1621 种不同的蛋白质。在这些蛋白质中,有 23 种蛋白质在 ZT18 小鼠中差异表达(p<0.05,倍数变化 1.4),其中 11 种上调(AKAP10、ALDOC、BLK、NCALD、NFL、PDE10A、PICAL、PSMB6、RL10、SH3L3 和 SYNJ1),12 种下调(AT2A2、AT2B1、CPNE5、KAP3、MAON、NPM、PI51C、PPR1B、SAM50、TOM70、TY3H 和 VAPA)。

讨论

总的来说,在这里我们鉴定了与昼夜节律相关的蛋白质,我们的进一步分析表明,这些蛋白质在分子功能、膜运输、生物发生、细胞过程、代谢过程以及帕金森病等神经退行性疾病中发挥着重要作用。

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