Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020438 (hypercalciuria)
 2,502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dent's disease, an X-linked tubulopathy secondary to defects in chloride channel CLC-5, is characterised by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal stones. Mechanisms leading to nephrocalcinosis are unknown. Using a murine collecting duct cell line (mIMCD-3), we confirm endogenous expression of mCLC-5. During transfection of antisense CLC-5, we observe a reduction in CLC-5 protein expression that correlates with a reduction in the number of acidic endosomal compartments, as determined by quantitative analysis of confocal microscope images using LysoTracker Red. Using wheat germ agglutinin-lectin as an endocytic marker, an arrest of endocytosis is observed in antisense CLC-5 treated cells. Exposure of the cell surface to calcium oxalate crystals results in crystal agglomeration in a minority of sense CLC-5 transfectants (45%) and all antisense CLC-5 transfectants. We conclude that expression of CLC-5 in mIMCD-3 cells allows acidification of endosomes and endocytosis, and that disruption of CLC-5 expression causes abnormal crystal agglomeration.
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PMID:Disordered calcium crystal handling in antisense CLC-5-treated collecting duct cells. 1250 84

Dent's disease, a renal tubular disorder characterized by low-molecular-weight proteinuria (LMWP), hypercalciuria, and nephrolithiasis, is due to inactivating mutations in the x-linked renal specific chloride channel CLC-5. CLC-5 belongs to the family of voltage-gated chloride channels, which function as homodimeric proteins with each subunit consisting of 18 helices and a chloride selectivity filter, i.e. pore. None of the 15 CLC-5 missense mutations reported in patients with dent's disease involves the chloride selectivity filter, but 12 of these are clustered around the interface of the two subunits, thereby emphasising the important role for the interaction between the two subunits at the interface of the homodimeric CLC-5. In the kidney, CLC-5 forms part of the receptor-mediated endocytic pathway, and defects in this pathway due to a loss of CLC-5 function, may help to account for the LMWP, hyperphosphaturia, hypercalciuria and nephrolithiasis. The molecular studies and the generation of mouse models of the disease have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis.
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PMID:Dent's disease--a nephrolithiasis disorder associated with defective receptor-mediated endocytosis. 1561 94