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猪视神经头和视网膜亚蛋白质组的比较定量分析。

Comparative Quantitative Analysis of Porcine Optic Nerve Head and Retina Subproteomes.

机构信息

Experimental and Translational Ophthalmology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.

Department of Urology and Pediatric Urology, University Medical Center, 55131 Mainz, Germany.

出版信息

Int J Mol Sci. 2019 Aug 29;20(17):4229. doi: 10.3390/ijms20174229.

Abstract

Optic nerve head (ONH) and retina (RET) are the main sites of damage in neurodegenerative optic neuropathies including glaucoma. Up to date, little is known about the molecular interplay between these two adjoining ocular components in terms of proteomics. To close this gap, we investigated ONH and RET protein extracts derived from porcine eyes ( = 12) ( Linnaeus 1758) using semi-quantitative mass spectrometry (MS)-based proteomics comprising bottom-up LC-ESI MS/MS and targeted SPE-MALDI-TOF MS analysis. In summary, more than 1600 proteins could be identified from the ONH/RET tissue complex. Moreover, ONH and RET displayed tissue-specific characteristics regarding their qualitative and semi-quantitative protein compositions. Gene ontology (GO)-based functional and protein-protein interaction analyses supported a close functional connection between the metabolic-related RET and the structural-associated ONH subproteomes, which could be affected under disease conditions. Inferred from the MS findings, stress-associated proteins including clusterin, ceruloplasmin, and endoplasmin can be proposed as extracellular mediators of the ONH/ RET proteome interface. In conclusion, ONH and RET show obvious proteomic differences reflecting characteristic functional features which have to be considered for future protein biomarker profiling studies.

摘要

视神经头(ONH)和视网膜(RET)是包括青光眼在内的神经退行性视神经病变的主要损伤部位。迄今为止,关于这两个毗邻眼组织在蛋白质组学方面的分子相互作用知之甚少。为了弥补这一空白,我们使用基于半定量质谱(MS)的蛋白质组学方法,包括自上而下的 LC-ESI MS/MS 和靶向 SPE-MALDI-TOF MS 分析,研究了源自猪眼(= 12)(Linnaeus 1758)的 ONH 和 RET 蛋白提取物。总之,我们可以从 ONH/RET 组织复合物中鉴定出 1600 多种蛋白质。此外,ONH 和 RET 在其定性和半定量蛋白质组成方面表现出组织特异性特征。基于基因本体论(GO)的功能和蛋白质-蛋白质相互作用分析支持代谢相关的 RET 和结构相关的 ONH 亚蛋白质组之间的密切功能联系,这些联系可能会在疾病状态下受到影响。根据 MS 研究结果,可以提出包括簇蛋白、铜蓝蛋白和内质网素在内的应激相关蛋白作为 ONH/RET 蛋白质组界面的细胞外介质。总之,ONH 和 RET 显示出明显的蛋白质组差异,反映了特征性功能特征,这在未来的蛋白质生物标志物分析研究中必须加以考虑。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e368/6747248/dcc7491af3a9/ijms-20-04229-g001.jpg

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