Mass spectrometric study of stone matrix proteins of human bladder stones.

OBJECTIVE

To evaluate the mechanisms of bladder uric acid stone (BUAS) formation by analyzing BUAS stone matrix proteins, with mass spectrometry (MS).

MATERIALS AND

METHODS

Stone matrix proteins were extracted from 5 pure BUASs. The obtained proteins were analyzed with reverse phase liquid chromatography-tandem MS. The acquired data were investigated against a Swiss Prot human protein database, using Matrix Science Mascot. The identified proteins were submitted to UniProtKB website for gene ontology analysis to define their correlation. They were also submitted to Metacore platform and Kyoto Encyclopedia of Genes and Genomes website for pathway analysis. MS-determined protein expressions were validated by immunoblot.

RESULTS

The liquid chromatography-tandem MS analysis identified 58-226 proteins in the 5 BUASs (450 proteins). Metacore software analysis suggests that inflammation might play an important role for BUAS formation. The analysis of endogenous metabolic pathways revealed that these proteins were categorized into glycerophospholipid or glycosphingolipid biosynthesis. Four of 5 identified proteins selected for validation, including uromodulin, S100P, Histone 4, and nucleophosmin, can be validated in the immunoblot data.

CONCLUSION

Our results suggest that inflammatory process and lipid metabolism might play a role in the formation of BUAS. Whether these inflammatory responses are the etiology of stone formation or whether they result from local damage by stone irritation is uncertain.