Data-Independent Acquisitions Uncover Kidney Proteome Remodeling during Ischemic Reperfusion Kidney Injury using a Fast-scanning ZenoTOF 7600
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ABSTRACT: 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.
INSTRUMENT(S): ZenoTOF 7600
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER: Birgit Schilling
PROVIDER: MSV000090777 | MassIVE | Wed Nov 23 11:51:00 GMT 2022
SECONDARY ACCESSION(S): PXD038339
REPOSITORIES: MassIVE
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