Abstract

The incidence/prevalence of kidney stone disease has been increasing around the globe but its pathogenic mechanisms remain unclear. Herein, we examined effects of oxidative modifications of urinary proteins on calcium oxalate (CaOx) crystallization, crystal growth and aggregation. Urinary proteins derived from 20 healthy individuals were modified by performic oxidation and the presence of oxidatively modified urinary proteins was verified, quantified and characterized by Oxyblot assay and tandem mass spectrometry (nanoLC-ESI-LTQ-Orbitrap-MS/MS). Subsequently, activities of oxidatively modified urinary proteins on CaOx crystallization, crystal growth and aggregation were evaluated. Both Oxyblot assay and nanoLC-ESI-LTQ-Orbitrap-MS/MS confirmed that urinary proteins were successfully oxidized by performic oxidation. The results showed that the oxidatively modified urinary proteins significantly promoted CaOx crystallization, crystal growth and aggregation. In contrast, the non-modified urinary proteins had inhibitory activities against CaOx crystallization, crystal growth and aggregation. These data indicate that oxidative modifications of urinary proteins increase the risk of kidney stone disease by promoting CaOx crystallization, crystal growth and aggregation.

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