Imaging mass spectrometry reveals direct albumin fragmentation within the diabetic kidney.

Kidney International
Kerri J GroveRichard M Caprioli

Abstract

Albumin degradation in the renal tubules is impaired in diabetic nephropathy such that levels of the resulting albumin fragments increase with the degree of renal injury. However, the mechanism of albumin degradation is unknown. In particular, fragmentation of the endogenous native albumin has not been demonstrated in the kidney and the enzymes that may contribute to fragmentation have not been identified. To explore this we utilized matrix-assisted laser desorption/ionization imaging mass spectrometry for molecular profiling of specific renal regions without disturbing distinct tissue morphology. Changes in protein expression were measured in kidney sections of eNOS-/-db/db mice, a model of diabetic nephropathy, by high spatial resolution imaging allowing molecular localizations at the level of single glomeruli and tubules. Significant increases were found in the relative abundances of several albumin fragments in the kidney of the mice with diabetic nephropathy compared with control nondiabetic mice. The relative abundance of fragments detected correlated positively with the degree of nephropathy. Furthermore, specific albumin fragments accumulating in the lumen of diabetic renal tubules were identified and predicted the enzy...Continue Reading

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Citations

Oct 18, 2020·Metabolomics : Official Journal of the Metabolomic Society·Zhen ChenShu-Ping Hui
Feb 21, 2019·ACS Medicinal Chemistry Letters·Robert W Johnson, Nari Talaty

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