Reliable Identification of Alpha2u-Globulin and Lysozyme Accumulation in Rat Kidney by Label-Free MALDI Mass Spectrometry Imaging

The molecular identification of alpha2 urinary protein in male rat kidneys is crucial in distinguishing human relevant from rat-specific cases of nephropathy caused by protein accumulation. As protein accumulation in the kidney presents uniformly as hyaline eosinophilic droplets, the identification of the causative protein can be very difficult, especially if suitable antibodies are lacking. We describe the successful identification of two morphologically similar protein accumulations (alpha2u protein and lysozyme) in rat kidneys by the matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI). The potential benefits of MSI may extend to other areas of toxicologic pathology, including instances where the protein accumulation must be characterized and the initial steps are unclear or the composition is unknown.