MassIVE MSV000090777

Partial Public PXD038339

Data-Independent Acquisitions Uncover Kidney Proteome Remodeling during Ischemic Reperfusion Kidney Injury using a Fast-scanning ZenoTOF 7600

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Description

Acute kidney injury (AKI) manifests as a major health concern particularly for the elderly and understanding related proteome changes is critical for prevention and development of novel therapeutics to recover kidney function, and to mitigate the susceptibility for recurrent AKI, or development of chronic kidney disease. In this study, mouse kidneys were subjected to ischemia-reperfusion injury while the contralateral kidneys remained uninjured to assess changes in the kidney proteome. A fast-scanning ZenoTOF 7600 mass spectrometer was used for comprehensive data-independent acquisition (DIA) for protein identification and quantification. Short microflow gradients, and the generation of a deep kidney-specific spectral library allowed for comprehensive and high-throughput assays. Upon AKI the kidney proteome was completely remodeled, and over half of the 3,945 quantified protein groups changed significantly. Downregulated proteins in the injured kidney were involved in energy production, including numerous peroxisomal matrix proteins, many related to lipid metabolism, such as ACOX1, CAT, EHHADH, ACOT4, ACOT8, and Scp2. Injured mice exhibited severely declined health. The comprehensive and sensitive kidney-specific DIA assays, highlighted in this work, feature high-throughput analytical capabilities to achieve deep coverage of the kidney proteome, and will serve as useful tool for the development of novel therapeutics aimed at remediating kidney function. [doi:10.25345/C5GQ6R662] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Acute Kidney Injury ; Data Independent Acquisition ; Fatty Acid Oxidation ; DIA ; Spectral Library ; Ischemic Reperfusion

Contact

Principal Investigators:
(in alphabetical order) 		Birgit Schilling, Buck Institute for Research on Aging, United States of America
Submitting User: jburton1

Publications

Burton JB, Silva-Barbosa A, Bons J, Rose J, Pfister K, Simona F, Gandhi T, Reiter L, Bernhardt O, Hunter CL, Goetzman ES, Sims-Lucas S, Schilling B.
Substantial downregulation of mitochondrial and peroxisomal proteins during acute kidney injury revealed by data-independent acquisition proteomics.
Proteomics. Epub 2023 Sep 29.

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