Abstract：
Zinc plays a crucial role both in the immune system and endocrine processes. Zinc restriction in the diet has been shown to lead to degeneration of the endocrine pancreas, resulting in hormonal imbalance within the β-cells. Proteostasismay vary depending on the stage of a pathophysiological process, which underscores the need for tools aimed at directly analyzing biological status. Among proteomics methods, MALDI-ToF-MS can serve as a rapid peptidomics tool for analyzing extracts or by histological imaging. Here we report the optimization of MALDI imaging mass spectrometry analysis of histological thin sections from mouse pancreas. This optimization enables the identification of the major islet peptide hormones as well as the major accumulated precursors and/or proteolytic products of peptide hormones. Cross-validation of the identified peptide hormones was performed by LC-ESI-MS from pancreatic islet extracts. Mice subjected to a zinc-restricted diet exhibited a relatively lower amount of peptide intermediates compared to the control group. These findings provide evidence for a complex modulation of proteostasis by micronutrients imbalance, a phenomenon directly accessed by MALDI-MSI.
摘要：
锌在免疫系统和内分泌过程中起着至关重要的作用。.饮食中的锌限制已被证明会导致内分泌胰腺退化，导致β细胞内的荷尔蒙失衡。蛋白质抑制可能根据病理生理过程的阶段而变化，这强调了对旨在直接分析生物学状态的工具的需求。在蛋白质组学方法中，MALDI-ToF-MS可以作为快速肽组学工具，用于分析提取物或通过组织学成像。在这里，我们报告了MALDI成像质谱分析小鼠胰腺组织学薄切片的优化。这种优化使得能够鉴定主要的胰岛肽激素以及肽激素的主要积累的前体和/或蛋白水解产物。通过来自胰岛提取物的LC-ESI-MS进行鉴定的肽激素的交叉验证。与对照组相比,接受锌限制饮食的小鼠表现出相对较低量的肽中间体。这些发现为微量营养素失衡对蛋白质平衡的复杂调节提供了证据，MALDI-MSI直接访问的现象。
