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Abstract: TH-PO884

Mass Spectrometry Imaging Reveals Alerted Metabolic Profiles of Small Molecules in Kidney Tissue Sections of Diabetic Mice

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Pamreddy, Annapurna, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Zhang, Guanshi, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Kim, Jiwan John, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Darshi, Manjula, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Velickovic, Dusan, Pacific Northwest National Laboratory, Richland, Washington, United States
  • Drel, Viktor, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States
  • Pasa-Tolic, Ljiljana, Pacific Northwest National Laboratory, Richland, Washington, United States
  • Alexandrov, Theodore, European Molecular Biology Laboratory, Heidelberg, Germany
  • Anderton, Christopher R., Pacific Northwest National Laboratory, Richland, Washington, United States
  • Sharma, Kumar, University of Texas Health Science Center at San Antonio, San Antonio, Texas, United States

Group or Team Name

  • Center for Renal Precision Medicine
Background

It was reported that 1,5-naphthlenediamine (1,5-DAN) hydrochloride assisted laser desorption ionization (LDI) mass spectrometry imaging (MSI) of kidneys, liver, and brain tissues 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).

Methods

In the current study, we employed a high resolution MALDI-MSI approach using 1,5-DAN hydrochloride as matrix to characterize small molecules in Akita (n = 3) and non-Akita (n = 3) mice kidney tissue sections at 20 μm spatial resolution. The data output was coupled to METASPACE for the annotation. SCiLS Lab and MetaboAnalyst were used for data processing and statistical analysis.

Results

In total, 107 metabolites were annotated by METASPACE in mice kidney tissue sections. MALDI MSI of kidney sections of F1 Akita mice clearly exhibited profound alterations of intermediates in the tricarboxylic acid cycle (TCA) cycle, glutamate-glutamine cycle, malate-aspartate shuttle, and phospholipid metabolism, simultaneously. Various metabolites underwent relatively remarkable changes in diabetic kidney tissues compared with the non-diabetic ones. Particularly, diabetic kidneys had higher relative abundance of glucose, xanthine and hypoxanthine, while lower relative levels of citric acid, glutamine, linoleic acid and arachidonic acid were observed.

Conclusion

In summary, MALDI-MSI is potentially effective and widespread application in small molecule in situ analysis of mice kidney tissues. MALDI-MSI technology coupled with METASPACE shed new light on our understanding of pathobiology of diabetic kidney disease.

Funding

  • NIDDK Support