Browsing by MeSH term "Calcium Phosphates"
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Publication Dietary phosphate restriction prevents the appearance of sarcopenia signs in old mice(Wiley, 2023-04) Alcalde-Estévez, Elena; Sosa, Patricia; Asenjo-Bueno, Ana; Plaza, Patricia; Valenzuela, Pedro L; Naves-Díaz, Manuel; Olmos, Gemma; López-Ongil, Susana; Ruiz-Torres, María P; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Gobierno del Principado de Asturias (España); European Union (EU); Instituto de Salud Carlos III; Ministerio de Ciencia, Innovación y Universidades (España); Comunidad de Madrid (España)BACKGROUND: Sarcopenia is defined by the progressive and generalized loss of muscle mass and function associated with aging. We have previously proposed that aging-related hyperphosphataemia is linked with the appearance of sarcopenia signs. Because there are not effective treatments to prevent sarcopenia, except for resistance exercise, we propose here to analyse whether the dietary restriction of phosphate could be a useful strategy to improve muscle function and structure in an animal model of aging. METHODS: Five-month-old (young), 24-month-old (old) and 28-month-old (geriatric) male C57BL6 mice were used. Old and geriatric mice were divided into two groups, one fed with a standard diet (0.6% phosphate) and the other fed with a low-phosphate (low-P) diet (0.2% phosphate) for 3 or 7ᅠmonths, respectively. A phosphate binder, Velphoroᆴ, was also supplemented in a group of old mice, mixed with a standard milled diet for 3ᅠmonths. Muscle mass was measured by the weight of gastrocnemius and tibial muscles, and quality by nuclear magnetic resonance imaging (NMRI) and histological staining assays. Muscle strength was measured by grip test and contractile properties of the tibialis muscle by electrical stimulation of the common peroneal nerve. Gait parameters were analysed during the spontaneous locomotion of the mice with footprinting. Orientation and motor coordination were evaluated using a static rod test. RESULTS: Old mice fed with low-P diet showed reduced serum phosphate concentration (16.46ᅠᄆᅠ0.77ᅠmg/dL young; 21.24ᅠᄆᅠ0.95ᅠmg/dL old; 17.46ᅠᄆᅠ0.82ᅠmg/dL low-P diet). Old mice fed with low-P diet displayed 44% more mass in gastrocnemius muscles with respect to old mice (Pᅠ=ᅠ0.004). NMRI revealed a significant reduction in T2 relaxation time (Pᅠ=ᅠ0.014) and increased magnetization transfer (Pᅠ=ᅠ0.045) and mean diffusivity (Pᅠ=ᅠ0.045) in low-P diet-treated mice compared with their coetaneous. The hypophosphataemic diet increased the fibre size and reduced the fibrotic area by 52% in gastrocnemius muscle with respect to old mice (Pᅠ=ᅠ0.002). Twitch force and tetanic force were significantly increased in old mice fed with the hypophosphataemic diet (Pᅠ=ᅠ0.004 and Pᅠ=ᅠ0.014, respectively). Physical performance was also improved, increasing gait speed by 30% (Pᅠ=ᅠ0.032) and reducing transition time in the static rod by 55% (Pᅠ=ᅠ0.012). Similar results were found when diet was supplemented with Velphoro. CONCLUSIONS: The dietary restriction of phosphate in old mice improves muscle quantity and quality, muscle strength and physical performance. Similar results were found using the phosphate binder Velphoro, supporting the role of phosphate in the impairment of muscle structure and function that occurs during aging.Publication Effect of sample time on urinary lithogenic risk indexes in healthy and stone-forming adults and children(BioMed Central (BMC), 2018-12-19) Rodríguez, Adrián; Saez-Torres, Concepcion; Mir Perelló, Maria Concepción; Casasayas-Carles, Paula; Rodriguez-Garcia, Nuria; Rodrigo, Dolores; Frontera-Juan, Guillem; Buades-Fuster, Juan Manuel; Gómez Cobo, Cristina; Costa-Bauza, Antonia; Grases, FelixBackground: The diagnosis and follow-up of stone forming patients is usually performed by analysis of 24-h urine samples. However, crystallization risk varies throughout the day, being higher at night. The main objective of this study is to evaluate the urinary crystallization risk in adults and children by calculating risk indexes based on different collection periods. Methods: The study included 149 adults (82 healthy and 67 stone-formers) and 108 children (87 healthy and 21 stone-formers). 24-h urine was collected, divided into 12-hdaytime sample (8am to 8pm), and 12-h overnight sample (8pm to 8am next morning). Solute concentrations, the calcium to citrate ratio (Ca/Cit), and the ion activity product of calcium oxalate (AP[CaOx]) and calcium phosphate (AP[CaP]) were calculated in each 12-h sample and in overall 24-h urine. Assessments were also related to stone type.ResultsCa/Cit and AP(CaOx) were significantly higher in stone forming patients than in healthy subjects. The 12-h overnight samples had the highest values for both risk indexes, confirming a greater risk for crystallization at night. The AP(CaP) index was significantly higher in patients with pure hydroxyapatite stones than healthy controls, but was not significantly different between stone-formers overall and healthy controls. Conclusions: The calculation of risk indexes is a simple method that clinicians can use to estimate crystallization risk. For this purpose, the use of 12-h overnight urine may be a reliable alternative to 24-h collections.Publication Na+ controls hypoxic signalling by the mitochondrial respiratory chain.(2020-10) Hernansanz-Agustín, Pablo; Choya-Foces, Carmen; Carregal-Romero, Susana; Ramos, Elena; Oliva, Tamara; Villa-Piña, Tamara; Moreno, Laura; Izquierdo-Álvarez, Alicia; Cabrera-García, J Daniel; Cortés, Ana; Lechuga-Vieco, Ana Victoria; Jadiya, Pooja; Navarro, Elisa; Parada, Esther; Palomino-Antolín, Alejandra; Tello, Daniel; Acin-Perez, Rebeca; Rodríguez-Aguilera, Juan Carlos; Navas, Plácido; Cogolludo, Ángel; López-Montero, Iván; Martínez-Del-Pozo, Álvaro; Egea, Javier; López, Manuela G; Elrod, John W; Ruíz-Cabello, Jesús; Bogdanova, Anna; Enriquez, Jose Antonio; Martínez-Ruiz, AntonioAll metazoans depend on the consumption of O2 by the mitochondrial oxidative phosphorylation system (OXPHOS) to produce energy. In addition, the OXPHOS uses O2 to produce reactive oxygen species that can drive cell adaptations1-4, a phenomenon that occurs in hypoxia4-8 and whose precise mechanism remains unknown. Ca2+ is the best known ion that acts as a second messenger9, yet the role ascribed to Na+ is to serve as a mere mediator of membrane potential10. Here we show that Na+ acts as a second messenger that regulates OXPHOS function and the production of reactive oxygen species by modulating the fluidity of the inner mitochondrial membrane. A conformational shift in mitochondrial complex I during acute hypoxia11 drives acidification of the matrix and the release of free Ca2+ from calcium phosphate (CaP) precipitates. The concomitant activation of the mitochondrial Na+/Ca2+ exchanger promotes the import of Na+ into the matrix. Na+ interacts with phospholipids, reducing inner mitochondrial membrane fluidity and the mobility of free ubiquinone between complex II and complex III, but not inside supercomplexes. As a consequence, superoxide is produced at complex III. The inhibition of Na+ import through the Na+/Ca2+ exchanger is sufficient to block this pathway, preventing adaptation to hypoxia. These results reveal that Na+ controls OXPHOS function and redox signalling through an unexpected interaction with phospholipids, with profound consequences for cellular metabolism.Publication A novel assay to measure calcification propensity: from laboratory to humans(Nature Publishing Group, 2020-10-16) Perez, M. Mar; Ferrer, Miguel D; Lazo-Rodriguez, Marta; Zeralda Canals, Ana; Banon-Maneus, Elisenda; Campistol, Josep M; Miller, Stephan; Garg, Rekha; Gold, Alex; Salcedo, Carolina; Perello, JoanCardiovascular calcification (CVC) contributes to morbidity and mortality in patients undergoing dialysis. We examined the pharmacodynamic effects of SNF472, a calcification inhibitor, on plasma calcium phosphate crystallization using spectrometric measurements, and its correlations with effects on CVC in rats or humans. Rats (N=38) injected with vitamin D (days 1-3) to induce CVC were infused with saline or SNF472 (days 1-12). Inhibition of CVC was 50-65% with SNF472 3 mg/kg and similar to 80% with SNF472 10 or 30 mg/kg. SNF472 dose-dependently inhibited calcium phosphate crystallization, which correlated with inhibition of CVC (r=0.628, P=0.005). In patients with calciphylaxis (N=14), infusion of SNF472 (similar to 7 mg/kg) during hemodialysis for 12 weeks inhibited calcium phosphate crystallization by nearly 70%. In patients with CVC (N=274), infusion of SNF472 during hemodialysis for 52 weeks inhibited calcium phosphate crystallization (placebo: 15%; 300 mg: 61%; 600 mg: 75%), which correlated with inhibition of CVC (r=0.401, P=0.003). These findings show a direct correlation between inhibition of calcium phosphate crystallization in plasma and inhibition of CVC both in a rat model and in humans, supporting the use of the pharmacodynamic assay in clinical trials as a potentially predictive tool to evaluate the activity of calcification inhibitors.Publication A novel pharmacodynamic assay to evaluate the effects of crystallization inhibitors on calcium phosphate crystallization in human plasma(Nature Publishing Group, 2017-07-31) Ferrer, MD; Perez, MM; Canaves, MM; Buades-Fuster, Juan Manuel; Salcedo, C; Perello, JCardiovascular calcification (CVC) is a progressive complication of chronic kidney disease and a predictor of CV events and mortality. The use of bionarkers to predict CV risk and activities of potential or current treatment drugs in these patients could have a crucial impact on therapeutic approaches. Our aim was to develop a novel assay for measurement of the rate of calcium phosphate crystallization in human plasma and provide a tool to evaluate the effects of crystallization inhibitors. The efficacy of inhibitors was determined by adding inhibitory compounds (polyphosphates, fetuin-A, sodium thiosulfate or citrate) to control samples. The assay was additionally validated for SNF472, an experimental formulation of phytate being developed for the treatment of calciphylaxis and CVC in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). The method was repeatable and reproducible. The plasma crystallization rate was reduced up to 80% in a concentration-dependent manner following treatment with inhibitors in vitro, among which SNF472 was the most potent. This method appears beneficial in evaluating and discriminating between inhibitory activities of compounds such as polyphosphates on calcium phosphate crystallization, which present a novel therapeutic approach to treat CVC in ESRD patients.Publication Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.(Public Library of Science (PLOS), 2015-12-15) Arrabal, Sergio; Lucena, Miguel Angel; Canduela, Miren Josune; Ramos-Uriarte, Almudena; Rivera, Patricia; Serrano, Antonia; Pavón, Francisco Javier; Decara, Juan; Vargas, Antonio; Baixeras, Elena; Martín-Rufián, Mercedes; Márquez, Javier; Fernández-Llébrez, Pedro; De Roos, Baukje; Grandes, Pedro; Rodríguez de Fonseca, Fernando; Suárez, Juan; [Arrabal,S; Lucena, MA; Rivera, P; Serrano,A; Pavón, FJ, Decara,J; Vargas,A; Baixeras,E; Rodriguez de Fonseca,F; Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica de Málaga (IBIMA). Universidad de Málaga. Hospital Universitario Regional de Málaga, Málaga, Spain. [Arrabal,S; Rivera, P; Serrano,A; Pavón, FJ, Decara,J; Vargas,A; Baixeras,E; Rodriguez de Fonseca,F; Suárez,J] CIBEROBN, Instituto de Salud Carlos III, Madrid, Spain. [Canduela,MJ; Ramos-Uriarte,A; Grandes,P] Department of Neurosciences, University of the Basque Country UPV/EHU, Leioa, Spain. [Martín-Rufián,M] ECAI de Proteómica, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Márquez,J] Departamento de Biología Molecular y Bioquímica, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [Fernández-Llébrez,P] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain. [De Roos,B] University of Aberdeen, Rowett Institute of Nutrition & Health, Aberdeen, United Kingdom.Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle--regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD.Publication Relationship between Urinary Level of Phytate and Valvular Calcification in an Elderly Population: A Cross-Sectional Study(Public Library of Science (PLOS), 2015-08-31) Fernandez-Palomeque, Carlos; Grau, Andres; Perello, Joan; Sanchis, Pilar; Isern, Bernat; Prieto, Rafael M; Costa-Bauza, Antonia; Caldes, Onofre J; Bonnin, Oriol; García-Raja, Ana; Bethencourt Gonzalez, Armando; Grases, FelixPathological calcification generally consists of the formation of solid deposits of hydroxyapatite (calcium phosphate) in soft tissues. Supersaturation is the thermodynamic driving force for crystallization, so it is believed that higher blood levels of calcium and phosphate increase the risk of cardiovascular calcification. However several factors can promote or inhibit the natural process of pathological calcification. This cross-sectional study evaluated the relationship between physiological levels of urinary phytate and heart valve calcification in a population of elderly out subjects. A population of 188 elderly subjects (mean age: 68 years) was studied. Valve calcification was measured by echocardiography. Phytate determination was performed from a urine sample and data on blood chemistry, end-systolic volume, concomitant diseases, cardiovascular risk factors, medication usage and food were obtained. The study population was classified in three tertiles according to level of urinary phytate: low (<0.610 mu M), intermediate (0.61-1.21 mu M), and high (>1.21 mu M). Subjects with higher levels of urinary phytate had less mitral annulus calcification and were less likely to have diabetes and hypercholesterolemia. In the multivariate analysis, age, serum phosphorous, leukocytes total count and urinary phytate excretion appeared as independent factors predictive of presence of mitral annulus calcification. There was an inverse correlation between urinary phytate content and mitral annulus calcification in our population of elderly out subjects. These results suggest that consumption of phytate-rich foods may help to prevent cardiovascular calcification evolution.