Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0451641 (urolithiasis)
 3,973 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. A broad spectrum of proteins has been detected within calcium stones. A newcomer to the field of urolithiasis is the blood protein inter-alpha-inhibitor. Inter-alpha-inhibitor comprises three protein chains linked by chondroitin sulphate: two heavy chains, H1 (65 kDa) and H2 (70 kDa) and a light chain (approx. 30 kDa) most commonly known as bikunin. The physiological function of the two heavy chains is unknown; nor has their presence been reported in urine. However, bikunin has been implicated in various renal diseases, including urolithiasis. 2. This study was undertaken to determine which chains of inter-alpha-inhibitor are actually present in calcium kidney stones. Organic extracts were obtained from 10 calcium stones and analysed by SDS/PAGE and Western blotting. The H1 and H2 chains of inter-alpha-inhibitor were detected in 9 of the 10 stones, but only one stone contained a protein with a molecular mass close to that of bikunin (30-35 kDa). 3. These results demonstrate for the first time that H1 and H2 are present in stones and show that the bikunin chain of inter-alpha-inhibitor may not be the only part of the molecule implicated in stone formation.
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PMID:Inter-alpha-inhibitor in calcium stones. 968 May 1

Our earlier studies indicated that members of the inter-alpha-inhibitor (IalphaI) family of glycoproteins may play an important role in urolithiasis. Indeed bikunin, the light chain of IalphaI is a potent inhibitor of calcium oxalate crystallization. In order to understand this role, the distribution of IalphaI and its related proteins, as well as the expression of bikunin, were studied in normal and nephrolithic rats. In normal rats, IalphaI immunoreactivity was located mainly in proximal tubules. However, in nephrolithic rats, in addition to proximal tubules, the staining was intensively extended to tubules in the corticomedullary junction. Furthermore, by using polymerase chain reaction technique, we demonstrated that gene encoding for bikunin was activated in kidneys of nephrolithic rats. We have previously demonstrated increased staining for osteopontin in association with calcium oxalate crystal deposition in rat kidneys. Others have shown an increase in osteopontin production by renal epithelial cells on exposure to calcium oxalate crystals. Based on these observations we conclude that kidney cells possess an auto-defense system against calcium oxalate crystallization and stone formation in which members of the IalphaI family may be closely involved.
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PMID:Role of inter-alpha-inhibitor and its related proteins in experimentally induced calcium oxalate urolithiasis. Localization of proteins and expression of bikunin gene in the rat kidney. 1009 55

The aim of this study was to compare the comprehensive intracrystalline protein profiles of calcium oxalate monohydrate (COM) and dihydrate (COD) crystals precipitated from the same human urine samples. Three separate batches of COM and COD crystals were precipitated from pooled healthy human urine by the addition of sodium oxalate at calcium concentrations of 2 and 8 mM, respectively. Proteins in whole extracts of demineralised COM and COD crystals, as well as in spots excised from 2D-PAGE gels of the extracts, were identified using liquid chromatography and tandem mass spectrometry (LC-MS/MS). The number and type of individual proteins differed between COM and COD: 14 substantive proteins were found inside COM crystal extracts and 34 inside COD, with 9 proteins occurring in both crystal types. Numerous keratins were detected. However, in line with consensus in the proteomics literature, as well as a lack of published evidence linking them to urolithiasis, they were excluded as contaminants, leaving very few consistently detected proteins. On the basis of their known association with stone disease or identification in multiple runs, the principal proteins in COM crystal extracts were prothrombin fragment 1, protein S100A9, and IGkappaV1-5, while those in extracts of COD crystals included osteopontin, IGkappaV1-5, protein S100A9, annexin A1, HMW kininogen-1, and inter-alpha-inhibitor (IalphaI). In general, proteins incorporated into both hydromorphs were acidic (pI<6), smaller than 55 kDa, and calcium binders. We concluded that the incorporation of proteins into urinary COM and COD crystals is selective and that only a few of the urinary proteins associated with the two hydromorphs are likely to play any significant role in stone pathogenesis.
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PMID:Comparison of the specific incorporation of intracrystalline proteins into urinary calcium oxalate monohydrate and dihydrate crystals. 2067 53