Effect of <i>Tamm-Horsfall </i>Protein on Calcium Oxalate Precipitation

Benković, Jasminka; Füredi-Milhofer, Helga; Hlady, Vladimir; Čvorišćec, Dubravka; Stavljenić-Rukavina, Ana

doi:10.1515/cclm.1995.33.10.705

Cited by 9 publications

(8 citation statements)

References 20 publications

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“…Many groups have investigated COM aggregation in the presence of both molecularly dispersed and aggregated THP without clearly identifying the role of protein aggregation in the promotion and/or inhibition of intercrystalline COM aggregation. As in this study, crystal aggregation promotion or loss of aggregation inhibition has been noted at conditions where aggregation of THP was presumed based on experimental conditions, but not determined definitively [2, 19, 20]. Others, however, have reported inhibition of COM aggregation at conditions where THP (with unspecified sialic acid content) remained molecularly dispersed in solution [19, 20, 50].…”

Section: Discussionmentioning

confidence: 72%

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

et al. 2011

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Tamm-Horsfall protein (THP) is thought to protect against calcium oxalate monohydrate (COM) stone formation by inhibiting COM aggregation. Several studies reported that stone formers produce THP with reduced levels of glycosylation, particularly sialic acid levels, which leads to reduced negative charge. In this study, normal THP was treated with neuraminidase to remove sialic acid residues, confirmed by an isoelectric point shift to higher pH. COM aggregation assays revealed that desialylated THP (ds-THP) promoted COM aggregation, while normal THP inhibited aggregation. The appearance of protein aggregates in solutions at ds-THP concentrations ≥1 µg/mL in 150 mM NaCl correlated with COM aggregation promotion, implying that ds-THP aggregation induced COM aggregation. The aggregation-promoting effect of the ds-THP was independent of pH above its isoelectric point, but was substantially reduced at low ionic strength, where protein aggregation was much reduced. COM aggregation promotion was maximized at a ds-THP to COM mass ratio of ~0.025, which can be explained by a model wherein partial COM surface coverage by ds-THP aggregates promotes crystal aggregation by bridging opposing COM surfaces, whereas higher surface coverage leads to repulsion between adsorbed ds-THP aggregates. Thus, desialylation of THP apparently abrogates a normal defensive action of THP by inducing protein aggregation, and subsequently COM aggregation, a condition that favors kidney stone formation.

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Section: Discussionmentioning

confidence: 72%

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

et al. 2011

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“…Aggregates of either native or desialylated THP induced COM crystal aggregation, while their molecularly-dispersed forms prevented crystal aggregation, as discussed below. Careful scrutiny of experimental conditions in many discordant results for THP [32, 62–67] suggests that the presence or absence of THP aggregates was likely an unrecognized variable in these experimental results.…”

Section: 0 Results and Discussionmentioning

confidence: 99%

The role of macromolecules in the formation of kidney stones

et al. 2016

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The formation of crystal aggregates, one of the critical processes in kidney stone pathogenesis, involves interactions between crystals (predominantly calcium oxalate monohydrate, COM) and urinary constituents (e.g. proteins), which serve as an adhesive “glue” between crystals in stones. To develop a better understanding of the protein-crystal interactions that lead to crystal aggregation, we have measured the effect of model proteins on bulk COM crystal properties as well as their adsorption on crystal surfaces using three synthetic polyanions: poly(aspartic acid) (polyD), poly(glutamic acid) (polyE), and poly(acrylic acid) (polyAA). These anionic macromolecules reduced the amount of COM crystal aggregation in bulk solution to an extent similar to that observed for mixture of proteins from normal urine, with little difference between the polymers. In contrast, the polymers exhibited differences in measures of COM crystal growth. Polycations such as poly(arginine) (polyR) and poly(lysine) (polyK) reduced aggregation weakly and exerted negligible effects on crystal growth. All polyions were found to associate with COM crystal surfaces, as evidenced by changes in the zeta potential of COM crystals in electrophoretic mobility measurements. On the other hand, COM aggregation and possibly growth can be promoted by many binary mixtures of polycations and polyanions, which appeared to be mediated by polymer aggregate formation rather than loss of crystal charge stabilization. Similarly, crystal aggregation promotion behavior can be driven by forming aggregates of weakly charged polyanions, like Tamm-Horsfall Protein, suggesting that polymer (protein) aggregation may play a critical role in stone formation. Sensitivity of polyanion–COM crystal surface interactions to the chemical composition of polymer side groups were demonstrated by large differences in crystal aggregation behavior between polyD and polyE, which correlated with atomic force microscopy (AFM) measurements of growth inhibition on various COM surfaces and chemical force microscopy (CFM) measurements of unbinding forces between COM crystal surfaces and AFM tips decorated with either carboxylate or amidinium moieties (mimicking polyanion and polyR side chains, respectively). The lack of strong interaction for polyE at the COM (100) surface compared to polyD appeared to be the critical difference. Finally, the simultaneous presence of polyanions and polycations appeared to alter the ability of polycations to mediate unbinding forces in CFM and promote crystal growth. In summary, polyanions strongly associated with COM surfaces and influenced crystallization, while polycations did not, though important differences were observed based on the physicochemical properties of polyanions. Observations suggest that COM aggregation with both polyanion–polycation mixtures and weakly charged polyanions is promoted by polymer aggregate formation, which plays a critical role in bridging crystal surfaces.

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“…Uromodulin is, in healthy individuals, the most abundant urinary protein (excretion rate approx. 50 mg/day) [3,4], where it is shown to have several beneficial effects including protection against ascending urinary tract infections [5] and prevention of renal stone formation [6,7]. 312 Uromodulin has also been shown to interact with components of the immune system generally associated with pro-inflammatory processes [8].…”

Section: Introductionmentioning

confidence: 99%

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

Schmid

Prajczer

Grüber

et al. 2010

Cell Physiol Biochem

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The glycosylated protein uromodulin is exclusively found in the thick ascending limb cells (TAL) of the kidney, where it is produced on mass and apically targeted, eventually being secreted into the urine. Recently, there has been a renewed interest in this protein due to its ability to interact with the immune system, implicating this protein as a renal inflammatory molecule. Here we investigated the potential role of membrane bound uromodulin on neutrophil adhesion and trans-epithelial migration. The renal tubular epithelial cell line, LLC-PK1, stably transfected with human uromodulin was used to investigate the influence of uromodulin on neutrophil adherence and migration. Uromodulin expression resulted in a significant increase of neutrophil adherence and trans-epithelial migration, in both the apical to basolateral and the basolateral to apical direction. Although uromodulin is GPI anchored and targeted to the apical membrane, we could also observe expression in the basal and lateral membranes domains, which may be responsible for basolateral to apical migration. Furthermore we show that uromodulin binds both the heavy and light chain of IgG, and that IgG enhances neutrophil migration. This study demonstrates that uromodulin can facilitate neutrophil trans-epithelial migration and that this migration can be amplified by co-factors such as IgG.

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Effect of Tamm-Horsfall Protein on Calcium Oxalate Precipitation

Cited by 9 publications

References 20 publications

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

Calcium oxalate monohydrate aggregation induced by aggregation of desialylated Tamm-Horsfall protein

The role of macromolecules in the formation of kidney stones

Uromodulin Facilitates Neutrophil Migration Across Renal Epithelial Monolayers

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