Cell cultures and nephrolithiasis

Verkoelen, Carl F.; Boom, Burt G. van der; Schröder, Fritz H.; Romijn, Johannes C.

doi:10.1007/bf01367660

Cited by 23 publications

(19 citation statements)

References 73 publications

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“…Urinary macromolecules, e.g. glycoproteins, proteins and glycosaminoglycans, adherent or bound to the crystals, counteract both crystal aggregation and crystal growth [12,20], and macromolecules are also important for the adherence of crystals to the tubular cells and for crystal-cell interaction [21,22].…”

Section: Epidemiological Considerationsmentioning

confidence: 99%

Epidemiology and medical management of stone disease

2003

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SUMMARYRecurrent stone formation in the urinary tract is a common and important problem that must be considered in daily urological practice. With a prevalence of> 10% and an expected recurrence rate of ≈ 50%, stone disease has an important effect on the healthcare system. It is generally agreed that patients with uric acid/urate, cystine or infection stones always should be treated pharmacologically. For calcium stone formers the treatment should be chosen according to the severity of the disease. Recurrence in patients with calcium‐stone disease can be prevented with general or specific dietary and drinking advice, and with pharmacological therapy. For idiopathic calcium stone formers the most convincing therapeutic effects have been reported with thiazide and alkaline citrate.

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Section: Epidemiological Considerationsmentioning

confidence: 99%

Epidemiology and medical management of stone disease

2003

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“…Several groups of investigators have suggested that an important early event in the formation of kidney stones is the attachment of calcium oxalate (CaOx) crystals to the apical surface of renal tubular epithelium (1)(2)(3). Well-polarized, undisturbed tubular epithelial cells in culture demonstrate little capacity for crystal attachment (4 -6).…”

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confidence: 99%

An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells

Сорокина¹,

Wesson²,

Kleinman³

2004

Journal of the American Society of Nephrology

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Abstract. Crystals that form in tubular fluid must be retained in the kidney to become stones. Nucleolin-related protein (NRP) is found on the surface of inner medullary collecting duct (IMCD) cells in culture (cIMCD) and selectively adsorbs to calcium oxalate (CaOx). We proposed that NRP mediates attachment to the renal tubular epithelium of Ca stone crystals through an electrostatic interaction with a highly acidic region (acidic fragment [AF]) similar to those of other proteins that have been reported to affect urinary crystal formation. The current studies demonstrate that nucleolin is expressed on both apical and basolateral cell surfaces of cIMCD, reaching a peak in the late stages of mitosis and gradually declining to undetectable levels with maturation of the polarized epithelium. Scraping areas of mature monolayers stimulated the cells surrounding the defects to migrate and proliferate so as to repair them, and these areas demonstrate surface NRP expression and enhanced attachment of CaOx monohydrate crystals. Surface expression of the NRP AF was produced by cloning the NRP AF into a display vector. Transfected cIMCD demonstrating copious surface expression of AF enhanced CaOx attachment 6.7-fold compared with control cIMCD, whereas cells transfected with a vector without the AF did not differ from control. AF was also cloned into a replication-deficient adenovirus and expressed in 293 cells, resulting in AF secretion into the nutrient medium. This medium inhibited CaOx attachment to cIMCD, compared with conditioned medium from cells infected with wild-type virus. These results demonstrate that surface-bound AF can mediate CaOx attachment and that secreted AF can inhibit attachment. These results support the notion that surface-associated NRP could mediate attachment of CaOx to the renal tubule epithelium, thereby causing retention of crystals that might eventually become kidney stones.Several groups of investigators have suggested that an important early event in the formation of kidney stones is the attachment of calcium oxalate (CaOx) crystals to the apical surface of renal tubular epithelium (1-3). Well-polarized, undisturbed tubular epithelial cells in culture demonstrate little capacity for crystal attachment (4 -6). This resistance to attachment may be due to the confinement of molecules with crystal-binding properties to domains other than the apical membrane. When tight junctions between cells are disrupted in the course of cellular proliferation or migration or when cells are exposed to a number of different agents, apical membranes seem to express constituents with affinity for CaOx.Nucleolin-related protein (NRP) is a surface-associated protein of cultured inner medullary collecting duct (IMCD) cells that selectively adsorbs to CaOx and binds to membrane skeletal elements in a Ca-dependent manner (7). NRP has a highly acidic region composed of 62% Asp and Glu residues (135KNGKNAKKEDSDEEDDDDSEEEDEEDEDEEDEFE PTVMKAAAAAPAS-DEEEDDEEDDDEDDDEEDEDED-EDDSEEEAMETTPAKGKKAPVKAVPVKAKSTAEE-DEEEDDEDEEDDEE...

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“…It has been reported that crystals interacting with the tubular epithelium lead to a retention and accumulation of crystalline material in the kidney and eventually to the development of a renal stone [20]. The mechanism is difficult to study in human subjects but is supported by several reports from cell cultures [21]. The most frequently associated phenomenon is tubular cell injury from high oxalate load in cell culture.…”

Section: Discussionmentioning

confidence: 79%

Effects of Tamm-Horsfall Protein and Albumin on the Inhibition of Free Radicals

Chen

Lin

Tsai³

et al. 2001

Urol Int

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Introduction: Oxalate in urine can cause tubular cellular damage by the production of free radicals. Then, cell death and cellular debris may promote the retention of calcium oxalate crystals and finally the formation of stones. The two most abundant urinary proteins, Tamm-Horsfall protein (THP) and albumin, were tested for the effects of antioxidants. Materials and Methods: By using xanthine-xanthine oxidase reaction, purified THP and albumin were tested for the inhibitory effect. OD₂₉₅ was used as a spectrophotometric method to measure the production of uric acid during the reaction. Results and Conclusions: Both proteins can inhibit the reaction of xanthine oxidase on xanthine, although the effect was decreased after enzymatic deglycosylation of sialic acid. Albumin has an IC₅₀ of 10.7 nM in native condition and 11.9 nM after deglycosylation, whereas THP has 69.6 nM in native condition and 102.0 nM in deglycosylated condition. The data indicates that THP and albumin have an antioxidant effect. Sialic acid in THP has partly an inhibitory effect and is associated with calcium oxalate formation. Studies have indicated that further investigation of the role of free radicals in the formation of urolithiasis and of sialic acid in protein function is needed.

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Cell cultures and nephrolithiasis

Cited by 23 publications

References 73 publications

Epidemiology and medical management of stone disease

Epidemiology and medical management of stone disease

An Acidic Peptide Sequence of Nucleolin-Related Protein Can Mediate the Attachment of Calcium Oxalate to Renal Tubule Cells

Effects of Tamm-Horsfall Protein and Albumin on the Inhibition of Free Radicals

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