Large-scale identification of calcium oxalate stone inhibitory proteins in normal human urine
Issued Date
2024-08-01
Resource Type
ISSN
01418130
eISSN
18790003
Scopus ID
2-s2.0-85197543039
Journal Title
International Journal of Biological Macromolecules
Volume
275
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Biological Macromolecules Vol.275 (2024)
Suggested Citation
Yoodee S., Peerapen P., Rattananinsruang P., Detsangiamsak S., Sukphan S., Thongboonkerd V. Large-scale identification of calcium oxalate stone inhibitory proteins in normal human urine. International Journal of Biological Macromolecules Vol.275 (2024). doi:10.1016/j.ijbiomac.2024.133646 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/99621
Title
Large-scale identification of calcium oxalate stone inhibitory proteins in normal human urine
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Recent evidence has shown that proteins in normal human urine can inhibit calcium oxalate (CaOx) kidney stone formation. Herein, we performed fast protein liquid chromatography (FPLC) to fractionate normal human urinary proteins using anion-exchange (DEAE) and size-exclusion (Superdex 200) materials. FPLC fractions (F1-F15) were examined by CaOx crystallization, growth, aggregation and crystal-cell adhesion assays. The fractions with potent inhibitory activities against CaOx crystals were then subjected to mass spectrometric protein identification. The data revealed that 13 of 15 fractions showed inhibitory activities in at least one crystal assay. Integrating CaOx inhibitory scores demonstrated that F6, F7 and F8 had the most potent inhibitory activities. NanoLC-ESI-Qq-TOF MS/MS identified 105, 93 and 53 proteins in F6, F7 and F8, respectively. Among them, 60 were found in at least two fractions and/or listed among known inhibitors with solid experimental evidence in the StoneMod database (https://www.stonemod.org). Interestingly, 10 of these 60 potential inhibitors have been reported with lower urinary levels in CaOx stone formers compared with healthy (non-stone) individuals, strengthening their roles as potent CaOx stone inhibitors. Our study provides the largest dataset of potential CaOx stone inhibitory proteins that will be useful for further elucidations of stone-forming mechanisms and ultimately for therapeutic/preventive applications.