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Kidney stone protein binding

Larisa Kovacevic, Hong Lu, Joseph A Caruso, Tuhina Govil-Dalela, Ronald Thomas, Yegappan Lakshmanan
BACKGROUND: Using a proteomic approach, we aimed to identify and compare the urinary excretion of proteins involved in lipid transport and metabolism in children with kidney stones and hypercalciuria (CAL), hypocitraturia (CIT), and normal metabolic work-up (NM), and in healthy controls (HCs). Additionally, we aimed to confirm these results using ELISA, and to examine the relationship between the urinary excretion of selected proteins with demographic, dietary, blood, and urinary parameters...
February 10, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Paleerath Peerapen, Visith Thongboonkerd
Recent large 3 cohorts have shown that caffeinated beverage consumption was associated with lower risk of kidney stone disease. However, its protective mechanisms remained unknown and had not been previously investigated. We thus evaluated protective effects of caffeine (1 μM-10 mM) on calcium oxalate monohydrate (COM) kidney stone formation, using crystallization, crystal growth, cell-crystal adhesion, Western blotting, and immunofluorescence assays. The results showed that caffeine reduced crystal number but, on the other hand, increased crystal size, resulting in unchanged crystal mass, consistent with crystal growth that was not affected by caffeine...
December 7, 2016: Scientific Reports
Kedsarin Fong-Ngern, Visith Thongboonkerd
To search for a strategy to prevent kidney stone formation/recurrence, this study addressed the role of α-enolase on apical membrane of renal tubular cells in mediating calcium oxalate monohydrate (COM) crystal adhesion. Its presence on apical membrane and in COM crystal-bound fraction was confirmed by Western blotting and immunofluorescence staining. Pretreating MDCK cells with anti-α-enolase antibody, not isotype-controlled IgG, dramatically reduced cell-crystal adhesion. Immunofluorescence staining also confirmed the direct binding of purified α-enolase to COM crystals at {121} > {100} > {010} crystal faces...
October 31, 2016: Scientific Reports
Nutkridta Pongsakul, Arada Vinaiphat, Prangwalai Chanchaem, Kedsarin Fong-Ngern, Visith Thongboonkerd
A previous study reported that lamin A/C (LMNA) expression was increased in renal tubular cells adhered with calcium oxalate monohydrate (COM) crystals; however, its functional significance in kidney stone disease remained unknown. In the present study, increased levels of LMNA and its partner, nesprin-1 (SYNE1), in Madin-Darby canine kidney cells upon COM crystal adhesion were confirmed by Western blotting and immunofluorescence staining. LMNA was then knocked down by small interfering RNA. Immunofluorescence staining confirmed the efficiency of small interfering RNA of LMNA (si-LMNA), which also reduced expression of its partner, SYNE1...
June 29, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Juthatip Manissorn, Visith Thongboonkerd
UNLABELLED: Heparin-binding proteins (HBPs) are considered as potential modulators of kidney stone formation. However, HBPs had not been characterized in the urine previously. In this study, we applied affinity purification-mass spectrometry (AP-MS) using cellufine sulfate column chromatography and liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-Q-TOF MS/MS) to identify HBPs in normal human urine. Using this approach, 83 HBPs were identified, including those involved in metabolic process, cellular process, immune system, developmental process, response to stimuli, cell communication, transport, cell adhesion and others...
June 16, 2016: Journal of Proteomics
Kedsarin Fong-Ngern, Kanyarat Sueksakit, Visith Thongboonkerd
Adhesion of calcium oxalate monohydrate (COM) crystals on renal tubular epithelial cells is a crucial step in kidney stone formation. Finding potential crystal receptors on the apical membrane of the cells may lead to a novel approach to prevent kidney stone disease. Our previous study identified a large number of crystal-binding proteins on the apical membrane of MDCK cells. However, their functional role as potential crystal receptors had not been validated. The present study aimed to address the potential role of heat shock protein 90 (HSP90) as a COM crystal receptor...
July 2016: Journal of Biological Inorganic Chemistry: JBIC
Hasan Fattah, Yasmin Hambaroush, David S Goldfarb
Our understanding of the molecular basis of cystinuria has deepened as the result of the causative genes, SLC3A1 and SLC7A9, being identified. The proteins coded for by these genes form a heterodimer responsible for reabsorption of filtered cystine in the proximal tubule. Failure of this transport system to be targeted to the apical membrane, as in the case of SLC3A1 mutations, or failure of the transport system to function, as in the case of SLC7A9 mutations, leads to abnormal urinary excretion of the relatively insoluble amino acid cystine...
September 1, 2014: Translational Andrology and Urology
Shigeru Shibata, Juan Pablo Arroyo, María Castañeda-Bueno, Jeremy Puthumana, Junhui Zhang, Shunya Uchida, Kathryn L Stone, TuKiet T Lam, Richard P Lifton
Hypertension contributes to the global burden of cardiovascular disease. Increased dietary K(+) reduces blood pressure; however, the mechanism has been obscure. Human genetic studies have suggested that the mechanism is an obligatory inverse relationship between renal salt reabsorption and K(+) secretion. Mutations in the kinases with-no-lysine 4 (WNK4) or WNK1, or in either Cullin 3 (CUL3) or Kelch-like 3 (KLHL3)--components of an E3 ubiquitin ligase complex that targets WNKs for degradation--cause constitutively increased renal salt reabsorption and impaired K(+) secretion, resulting in hypertension and hyperkalemia...
October 28, 2014: Proceedings of the National Academy of Sciences of the United States of America
Tao Na, Ji-Bin Peng
TRPV5 is one of the two channels in the TRPV family that exhibit high selectivity to Ca(2+) ions. TRPV5 mediates Ca(2+) influx into cells as the first step to transport Ca(2+) across epithelia. The specialized distribution in the distal tubule of the kidney positions TRPV5 as a key player in Ca(2+) reabsorption. The responsiveness in expression and/or activity of TRPV5 to hormones such as 1,25-dihydroxyvitamin D3, parathyroid hormone, estrogen, and testosterone makes TRPV5 suitable for its role in the fine-tuning of Ca(2+) reabsorption...
2014: Handbook of Experimental Pharmacology
Yi-Lei Wu, Daw-Yang Hwang, Hui-Pin Hsiao, Wei-Hsin Ting, Chi-Yu Huang, Wen-Yu Tsai, Hung-Chun Chen, Mei-Chyn Chao, Fu-Sung Lo, Jeng-Daw Tsai, Stone Yang, Shin-Lin Shih, Shuan-Pei Lin, Chiung-Ling Lin, Yann-Jinn Lee
An inactivating mutation in the GNAS gene causes either pseudohypoparathyroidism 1a (PHP1A) when it is maternally inherited or pseudopseudohypoparathyroidism (PPHP) when it is paternally inherited. We investigated clinical manifestations and mutations of the GNAS gene in ethnic Chinese patients with PHP1A or PPHP. Seven patients from 5 families including 4 girls and 2 boys with PHP1A and 1 girl with PPHP were studied. All PHP1A patients had mental retardation. They were treated with calcitriol and CaCO3 with regular monitoring of serum Ca levels, urinary Ca/Cr ratios, and renal sonography...
2014: PloS One
Maria Goiko, Joshua Dierolf, Jared S Gleberzon, Yinyin Liao, Bernd Grohe, Harvey A Goldberg, John R de Bruyn, Graeme K Hunter
Matrix Gla protein (MGP) is a phosphorylated and γ-carboxylated protein that has been shown to prevent the deposition of hydroxyapatite crystals in the walls of blood vessels. MGP is also expressed in kidney and may inhibit the formation of kidney stones, which mainly consist of another crystalline phase, calcium oxalate monohydrate. To determine the mechanism by which MGP prevents soft-tissue calcification, we have synthesized peptides corresponding to the phosphorylated and γ-carboxylated sequences of human MGP in both post-translationally modified and non-modified forms...
2013: PloS One
Kanu Priya Aggarwal, Simran Tandon, Pradeep Kumar Naik, Shrawan Kumar Singh, Chanderdeep Tandon
BACKGROUND: The increasing number of patients suffering from urolithiasis represents one of the major challenges which nephrologists face worldwide today. For enhancing therapeutic outcomes of this disease, the pathogenic basis for the formation of renal stones is the need of hour. Proteins are found as major component in human renal stone matrix and are considered to have a potential role in crystal-membrane interaction, crystal growth and stone formation but their role in urolithiasis still remains obscure...
2013: PloS One
Nilubon Singhto, Kitisak Sintiprungrat, Visith Thongboonkerd
The presence of macrophages in renal interstitium is the key feature of progressive renal inflammation in kidney stone disease. However, response of macrophages to calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stone, remained unclear. This study aimed to investigate alterations in the cellular proteome of macrophages induced by COM crystals using a proteomics approach. U937-derived macrophages (by phorbol-12-myristate-13-acetate activation) were incubated without or with 100 μg/mL COM crystals for 24 h...
August 2, 2013: Journal of Proteome Research
Yasuhiko Hirose, Takahiro Yasui, Kazumi Taguchi, Yasuhiro Fujii, Kazuhiro Niimi, Shuzo Hamamoto, Atsushi Okada, Yasue Kubota, Noriyasu Kawai, Yasunori Itoh, Keiichi Tozawa, Shoichi Sasaki, Kenjiro Kohri
Renal tubular cell injury induced by oxalate plays an important role in kidney stone formation. Water containing oxygen nano-bubbles (nanometer-sized bubbles generated from oxygen micro-bubbles; ONB) has anti-inflammatory effects. Therefore, we investigated the inhibitory effects of ONB water on kidney stone formation in ethylene glycol (EG)-treated rats. We divided 60 rats, aged 4 weeks, into 5 groups: control, the water-fed group; 100 % ONB, the 100 % ONB water-fed group; EG, the EG treated water-fed group; EG + 50 % ONB and EG + 100 % ONB, water containing EG and 50 % or 100 % ONB, respectively...
August 2013: Urolithiasis
Armando L Negri, Francisco R Spivacow, Elisa E Del Valle
The composition of urine is influenced by diet and changes in dietary factors have been proposed to modify the risk of recurrent nephrolithiasis. Nutrients that have been implicated include calcium, oxalate, sodium, animal protein, magnesium and potassium. There is significant evidence showing that a high calcium diet is associated with a reduction of lithogenic risk. One of the possible mechanisms to explain this apparent paradox is that the higher intake of calcium in the intestine binds with dietary oxalate, reducing its absorption and urinary excretion...
2013: Medicina
Rattiyaporn Kanlaya, Kitisak Sintiprungrat, Visith Thongboonkerd
Kidney stone disease is associated with renal fibrosis by the unclear mechanisms. We hypothesized that calcium oxalate (CaOx), a major crystalline component of kidney stones, could induce secretion of fibrotic factors from macrophages leading to "epithelial mesenchymal transition/transdifferentiation" (EMT) of renal tubular cells. Western blot analysis revealed an increased level of vimentin (mesenchymal marker) but decreased levels of E-cadherin and cytokeratin (epithelial markers) in MDCK cells treated with "secreted products from CaOx-exposed macrophages" (CaOx-M-Sup)...
2013: Cell Biochemistry and Biophysics
Shigeru Shibata, Junhui Zhang, Jeremy Puthumana, Kathryn L Stone, Richard P Lifton
Pseudohypoaldosteronism type II (PHAII) is a rare Mendelian syndrome featuring hypertension and hyperkalemia resulting from constitutive renal salt reabsorption and impaired K(+) secretion. Recently, mutations in Kelch-like 3 (KLHL3) and Cullin 3 (CUL3), components of an E3 ubiquitin ligase complex, were found to cause PHAII, suggesting that loss of this complex's ability to target specific substrates for ubiquitination leads to PHAII. By MS and coimmunoprecipitation, we show that KLHL3 normally binds to WNK1 and WNK4, members of WNK (with no lysine) kinase family that have previously been found mutated in PHAII...
May 7, 2013: Proceedings of the National Academy of Sciences of the United States of America
Annual incidences of kidney stones are about 0.1- 0.4% of the population, and lifetime prevalences in the USA and Europe range between 8 and 15%. Kidney stones occur more frequently with increasing age and among men. Within ten years, the disease usually recurs in more than 50% of patients. Nowadays, about 85% of all kidney stones contain calcium salts (calcium oxalate and/or calcium phosphate) as their main crystalline components. Because human urine is commonly supersaturated with respect to calcium salts as well as to uric acid, crystalluria is very common, i...
February 1, 2003: Therapeutische Umschau. Revue Thérapeutique
Aslam Khan, Wei Wang, Saeed R Khan
OBJECTIVES: Polymorphism of the gene for matrix GLA protein (MGP), a calcification inhibitor, is associated with nephrolithiasis. However, experimental investigations of MGP role in stone pathogenesis are limited. We determined the effect of renal epithelial exposure to oxalate (Ox), calcium oxalate (CaOx) monohydrate (COM) or hydroxyapatite (HA) crystal on the expression of MGP. METHODS: MDCK cells in culture were exposed to 0.3, 0.5 or 1 mM Ox and 33, 66 or 133-150 μg/cm(2) of COM/HA for 3-72 h...
February 2014: World Journal of Urology
Eric Chabriere, Mikael Elias, Julien Hiblot, Ahmed Djeghader, Christian Schwartz, Olivier Rohr, Patrick Masson
DING proteins comprise an intriguing phosphate-binding protein family present in all animal phyla. Five different DING representatives have been described in humans. Eukaryotic DING proteins are mostly involved in cellular processes such as cell cycle regulation, and also in pathological process such as rheumatoid arthritis and kidney stone formation. Although these proteins are ubiquitous in eukaryotes, no relevant locus or ORF has yet been found in sequenced genomes. This lack of sequence information has considerably hampered functional and structural studies of these proteins, and has required the use of novel and original techniques such as ab initio protein sequencing based on a combination of X-ray crystallography and mass spectrometry...
March 2012: Bulletin de L'Académie Nationale de Médecine
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