Substantial downregulation of mitochondrial and peroxisomal proteins during acute kidney injury revealed by data-independent acquisition proteomics.
Jordan B BurtonAnne Silva-BarbosaJoanna BonsJacob RoseKatherine PfisterFabia SimonaTejas GandhiLukas ReiterOliver BernhardtChristie L HunterEric S GoetzmanSunder Sims-LucasBirgit SchillingPublished in: Proteomics (2023)
Acute kidney injury (AKI) manifests as a major health concern, particularly for the elderly. Understanding AKI-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, and the contralateral kidneys remained uninjured to enable comparison and assess injury-induced changes in the kidney proteome. A ZenoTOF 7600 mass spectrometer was optimized for data-independent acquisition (DIA) to achieve comprehensive protein identification and quantification. Short microflow gradients and the generation of a deep kidney-specific spectral library allowed for high-throughput, comprehensive protein quantification. Upon AKI, the kidney proteome was completely remodeled, and over half of the 3945 quantified protein groups changed significantly. Downregulated proteins in the injured kidney were involved in energy production, including numerous peroxisomal matrix proteins that function in fatty acid oxidation, such as ACOX1, CAT, EHHADH, ACOT4, ACOT8, and Scp2. Injured kidneys exhibited severely damaged tissues and injury markers. The comprehensive and sensitive kidney-specific DIA-MS assays feature high-throughput analytical capabilities to achieve deep coverage of the kidney proteome, and will serve as useful tools for developing novel therapeutics to remediate kidney function.
Keyphrases
- acute kidney injury
- high throughput
- cardiac surgery
- chronic kidney disease
- ischemia reperfusion injury
- fatty acid
- small molecule
- oxidative stress
- gene expression
- mass spectrometry
- healthcare
- public health
- protein protein
- computed tomography
- multiple sclerosis
- electronic health record
- ms ms
- hydrogen peroxide
- single cell
- big data
- end stage renal disease
- mental health
- nitric oxide
- machine learning
- magnetic resonance imaging
- peritoneal dialysis
- risk assessment
- health information
- amino acid
- middle aged
- social media
- community dwelling
- dual energy
- affordable care act