MALDI imaging mass spectrometry to investigate endogenous peptides in an animal model of Usher's disease
MALDI imaging mass spectrometry to investigate endogenous peptides in an animal model of Usher's disease
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DOI：
10.1002/pmic.201300558
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发表时间：
2014-07-01
期刊：
影响因子：
3.4
通讯作者：
Pich, Andreas
中科院分区：
文献类型：
--
作者：
Chatterji, Bijon;Dickhut, Clarissa;Pich, Andreas
成像MS（MSI）已成为研究脑中生物分子空间分布的有价值的工具。本文中，MALDI-MSI用于确定内源性肽在Usher病大鼠模型中的分布。这种罕见的疾病被认为是世界范围内人类失明的主要原因。通过MALDI-MSI分析脑组织冷冻切片以区分健康和患病大鼠。MSI结果具有高度可重复性。使用LC-Orbitrap和MALDI-TOF/TOF分析通过MS/MS鉴定组织特异性肽。由于这些肽在脑中的特定空间分布，例如，黑质、胼胝体和海马体，因此提出了这些肽用于组织学分类。几种内源性肽显示出显著增加的离子密度，特别是在上丘和患病大鼠的黑质中，包括来自Fsd 1、肌营养不良蛋白-β和ProSAAS的肽。此外，髓鞘碱性蛋白的几种蛋白水解降解产物被鉴定，其中一种肽最有可能由钙蛋白酶-2介导。我们的研究结果有助于这种动物模型的表征，包括可能的疾病肽标志物。
Imaging MS (MSI) has emerged as a valuable tool to study the spatial distribution of biomolecules in the brain. Herein, MALDI-MSI was used to determine the distribution of endogenous peptides in a rat model of Usher's disease. This rare disease is considered as a leading cause of deaf-blindness in humans worldwide. Cryosections of brain tissue were analyzed by MALDI-MSI to differentiate between healthy and diseased rats. MSI results were highly reproducible. Tissue-specific peptides were identified by MS/MS using LC-Orbitrap and MALDI-TOF/TOF analyses. These peptides were proposed for histological classification due to their particular spatial distribution in the brain, for example, substantia nigra, corpus callosum, and hippocampus. Several endogenous peptides showed significantly increased ion densities, particularly in the colliculi superiores and in the substantia nigra of diseased rats, including peptides derived from Fsd1, dystrobrevin-beta, and ProSAAS. Furthermore, several proteolytic degradation products of the myelin basic protein were identified, of which one peptide is most likely mediated by calpain-2. Our findings contribute to the characterization of this animal model and include possible peptide markers of disease.