Topic: IMSS Special Topics
Authors: Annapurna Pamreddy,* Guanshi Zhang,*† Jiwan Kim,*† Manjula Darshi,*† Jessica Lukowski,‡ Dusan Velikovic,‡ Ljiljana Pasa-Tolic,‡ Christopher Anderton,*‡ Theodore Alexandrov,||¶ Kumar Sharma.*†
In clinical applications, mass spectrometry imaging (MSI) is mostly concerned with the analysis of thin tissue sections from patient material where mass spectrometric data is acquired in a spatially resolved manner by aligning the ionization source to distinct spots on the sample’s surface. The ability of MSI to localize panels of biomolecules in tissues, without prior knowledge of their presence and in a label-free manner, has led to a rapid and substantial impact in clinical research, uncovering biomolecular changes associated with disease and providing low cost imaging of various molecules (Addie, Ruben D., et al., 2015). Small molecules could provide biological insights via MSI of kidneys, liver, and brain tissues for a variety of disease states. It was reported that MSI allowed to visualize the spatial distribution and alteration of a broad range of small molecule metabolites including metal ions, amino acids, carboxylic acids, nucleotide derivatives, peptides, and lipids simultaneously. MSI has potential applications in small molecule in situ analysis (Huihui Liu et al., 2014).
In the current study, we employed a high resolution matrix-assisted laser desorption/ionization (MALDI)-MSI approach using an organic salt as matrix to characterize small molecules in Akita (n = 6) and non-Akita (n = 6) mice kidney tissue sections at 20 - 30 μm spatial resolution. The data output was coupled to METASPACE for the putative molecular annotations. SCiLS Lab and MetaboAnalyst were used for data processing and statistical analysis.
In total, 256 metabolites were annotated by METASPACE (using the HMDB database) in mice kidney tissue sections. MALDI-MSI of kidney sections of F1 Akita mice clearly exhibited profound alterations in species putatively annotated as intermediates in the tricarboxylic acid cycle (TCA) cycle, glutamate-glutamine cycle, malate-aspartate shuttle, and phospholipid metabolism, simultaneously. A number of various metabolites exhibited marketable differences in abundances in diabetic kidney tissues in comparison to the non-diabetic ones. Particularly, diabetic kidneys had higher relative abundance of glucose, xanthine and hypoxanthine, while lower relative abundances of citric acid, glutamine, linoleic acid and arachidonic acid were observed.
Newly optimized MALDI-MSI method permitted us to visualize the spatial distribution of a broad range of small metabolites markers involved in tricarboxylic acid (TCA) cycle, glutamate-glutamine cycle, and malate-aspartate shuttle, together with metal ions and phospholipids in mice kidney cortex tissue. MALDI-MSI technology coupled with METASPACE shed new light on our understanding of pathobiology of diabetic kidney disease.
|Salary||yes||University of Texas Health Science Center, San Antonio|
|Planning to mention or discuss specific products or technology of the company(ies) listed above:||