MSACL 2020 US Abstract

Altered Metabolic Profiles of Small Molecule Map of Diabetic Mice Kidney Tissue Revealed by Mass Spectrometry Imaging

Annapurna Pamreddy,* Guanshi Zhang,*† Jiwan Kim,*† Manjula Darshi,*† Jessica Lukowski,‡ Dusan Velikovic,‡ Ljiljana Pasa-Tolic,‡ Christopher Anderton,*‡ Theodore Alexandrov,||¶ Kumar Sharma.*†
*Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine, The University of Texas Health San Antonio, TX, USA; †Audie L. Murphy Memorial VA Hospital, South Texas Veterans Health Care System, San Antonio, TX, USA; ‡Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, USA; ||Structural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany; and ¶Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA. Corresponding author: E-mail: sharmak3@uthscsa.edu

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Annapurna Pamreddy (Presenter) University of Texas Health Science Center

Presenter Bio: Biographical Sketch – Annapurna Pamreddy
Vitae

College: B.Sc., Microbiology, Genetics, Chemistry, 2002, Osmania University, India
Graduate Degrees: M.Sc. Chemistry, 2006, Acharya Nagarjuna University, India
M.Sc. Analytical Chemistry, 2008, Osmania University, India
Ph.D.: Analytical Chemistry, 2014, Masaryk University, Czech Republic
Postdoctoral: 1. Postdoctoral Research Associate, Kwazulu-Natal University,
South Africa, July 2016 – June 2018.
2. Postdoctoral Research Associate, Durban University of
Technology, South Africa, June 2018 – December 2018.
3. Postdoctoral Research Associate, University of Texas Health,
San Antonio, Texas, USA, Feb 2019 – Present.

a) Professional:
Laxmi Genchem Sciences Pvt. Ltd. Hyderabad, India, 2015- 2016
MSN Laboratories Pvt. Ltd., Hyderabad, India, 2008-2010

b) Products:

i) Products

1. A. Pamreddy, Sooraj Baijnath

Relevant Financial Disclosures (within past 24 months) Grant/Research Support KPMP Salary University of Texas Health Science Center, San Antonio Conflict mitigation NOT REQUIRED.

BACKGROUND:
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).
METHODS:
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.
RESULTS:
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.
CONCLUSION:
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.