Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag
Development of an On-Tissue Derivatization Method for MALDI Mass Spectrometry Imaging of Bioactive Lipids Containing Phosphate Monoester Using Phos-tag
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DOI：
10.1021/acs.analchem.0c04479
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发表时间：
2021-02-12
影响因子：
7.4
通讯作者：
Aoki, Junken
中科院分区：
文献类型：
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作者：
Iwama, Taiga;Kano, Kuniyuki;Aoki, Junken
基质辅助激光解吸电离质谱成像（MALDI-MSI）是一种新兴的无标记方法，用于绘制组织切片中不同分子种类的分布。尽管最近在脂质的MALDI-MSI分析方面取得了进展，但仍然难以可视化包括溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1 P）在内的次要生物活性脂质。在这里，我们已经开发了一种新的组织衍生化方法，使用Phos标签，锌复合物，特异性结合到磷酸单酯基团。具有Phos-标签衍生化的MALDI-MSI使得有可能在小鼠脑中成像LPA和S1 P。此外，我们能够看到其他低丰度脂质含有磷酸单酯，如磷脂酸和神经酰胺-1-磷酸。与传统的MALDI-MS相比，这种衍生化产生的LPA图像具有高空间精度，可以区分MALDI-MS分析过程中人为产生的LPA。在缺乏降解LPA和S1 P的酶的小鼠中，我们观察到S1 P和/或LPA在大脑特定区域的显著积累。因此，本研究提供了一种简单而最佳的方法来揭示有效的生物活性脂磷酸盐，如LPA和S1 P在组织中的空间定位。
Matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) is an emerging label-free method for mapping the distribution of diverse molecular species in tissue sections. Despite recent progress in MALDI-MSI analyses of lipids, it is still difficult to visualize minor bioactive lipids including lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Here, we have developed a novel on-tissue derivatization method using Phos-tag, a zinc complex that specifically binds to a phosphate monoester group. MALDI-MSI with Phos-tag derivatization made it possible to image LPA and S1P in the murine brain. Furthermore, we were able to visualize other low-abundance lipids containing phosphate monoester, such as phosphatidic acid and ceramide-1-phosphate. Compared with conventional MALDI-MS, this derivatization produced LPA images with high spatial accuracy discriminating LPA artificially produced during MALDI-MS analysis. In mice with deficiencies in enzymes that degrade LPA and S1P, we observed marked S1P and/or LPA accumulation in specific regions of the brain. Thus, the present study provides a simple and optimal way to reveal the spatial localization of potent bioactive lipid phosphates such as LPA and S1P in tissues.