Longitudinal study of urinary excretion of phosphate, calcium, and uric acid in mutant NHERF-1 null mice

2006 ◽  
Vol 290 (4) ◽  
pp. F838-F843 ◽  
Author(s):  
Edward J. Weinman ◽  
Viresh Mohanlal ◽  
Nicholas Stoycheff ◽  
Fengying Wang ◽  
Deborah Steplock ◽  
...  
Keyword(s):  
Uric Acid ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Young Male ◽  
Wild Type ◽  
Protein Targets ◽  
Male And Female ◽  
Age Related ◽  
Time Period ◽  
Apical Membranes

NHERF-1 binds numerous renal protein targets, including the proximal tubule transporters Na+/H+ exchanger 3 (NHE3) and Na+-phosphate cotransporter 2a (Npt2a). Young NHERF-1−/− male mice display defective targeting of Npt2a to apical membranes in the renal proximal tubule and manifest hypophosphatemia and increased urinary excretion of phosphate. The present studies describe the changes in the urinary excretion of phosphate, calcium, uric acid, and sodium in male and female wild-type and NHERF-1 null mice over a time period from 12 to 54 wk of age. Young male and female NHERF-1−/− mice demonstrated increased urinary excretion of phosphate and urine phosphate/creatinine ratios. There was an age-related decline in the phosphate/creatinine ratio in mutant mice such that there were no differences between wild-type and NHERF-1−/− by 24 to 30 wk of age despite the continued presence of hypophosphatemia. Male and female NHERF-1 null mice also demonstrate increased urine calcium/creatinine and uric acid/creatinine ratios compared with wild-type controls. These studies indicate defects in the renal tubule transport of phosphate, calcium, and uric acid in NHERF-1−/− male and female mice that could account for the increased deposition of calcium in the papilla of null mice.

Urine electrolyte, mineral, and protein excretion in NHERF-2 and NHERF-1 null mice

2008 ◽  
Vol 294 (4) ◽  
pp. F1001-F1007 ◽  
Author(s):  
Rochelle Cunningham ◽  
Ali Esmaili ◽  
Eric Brown ◽  
Rajat S. Biswas ◽  
Rakhilya Murtazina ◽  
...  
Keyword(s):  
Uric Acid ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Adaptor Proteins ◽  
Renal Proximal Tubule ◽  
Wild Type ◽  
Sodium Hydrogen Exchanger ◽  
Model Cell ◽  
Abundance And Distribution ◽  
Wild Type Control

The adaptor proteins sodium/hydrogen exchanger regulatory factor (NHERF)-1 and NHERF-2 have overlapping tissue distribution in renal cells and overlapping specificity in their binding to renal transporters and other proteins. To compare the kidney-specific differences in the function of these adaptor proteins, NHERF-1 and NHERF-2 null mice were compared with wild-type control mice. In NHERF-2 null mice, the renal proximal tubule abundance and distribution of NHERF-1 and NHERF-3 were not different from those in wild-type animals. The glomerular expression of podocalyxin and ZO-1 also did not differ. NHERF-1 null mice had increased urinary excretion of phosphate, calcium, and uric acid compared with wild-type control and NHERF-2 null mice. Because of the association between NHERF-2 and podocalyxin in glomeruli and ClC-5 in the renal proximal tubule, the urinary excretion of protein was determined. There were no differences in the urinary excretion of protein or low-molecular-weight proteins between wild-type control, NHERF-1−/−, and NHERF-2−/− mice. These studies indicate that the increased urinary excretion of phosphate and uric acid are specific to NHERF-1 null mice and highlight the fact that predictions about the role of adaptor proteins such as the NHERF proteins obtained from studies of model cell systems must be confirmed in whole animals.

scholarly journals NPY Deficiency Prevents Postmenopausal Adiposity by Augmenting Estradiol-Mediated Browning

2018 ◽  
Vol 75 (6) ◽  
pp. 1042-1049
Author(s):  
Seongjoon Park ◽  
Erkhembayar Nayantai ◽  
Toshimitsu Komatsu ◽  
Hiroko Hayashi ◽  
Ryoichi Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Fat Metabolism ◽  
Male Mice ◽  
Wild Type ◽  
Male And Female ◽  
Female Mice ◽  
Age Related ◽  
Promising Target ◽  
Intracellular Mechanism

Abstract The orexigenic hormone neuropeptide Y (NPY) plays a pivotal role in the peripheral regulation of fat metabolism. However, the mechanisms underlying the effects of sex on NPY function have not been extensively analyzed. In this study, we examined the effects of NPY deficiency on fat metabolism in male and female mice. Body weight was slightly decreased, whereas white adipose tissue (WAT) mass was significantly decreased as the thermogenic program was upregulated in NPY-/- female mice compared with that in wild-type mice; these factors were not altered in response to NPY deficiency in male mice. Moreover, lack of NPY resulted in an increase in luteinizing hormone (LH) expression in the pituitary gland, with concomitant activation of the estradiol-mediated thermogenic program in inguinal WAT, and alleviated age-related modification of adiposity in female mice. Taken together, these data revealed a novel intracellular mechanism of NPY in the regulation of fat metabolism and highlighted the sexual dimorphism of NPY as a promising target for drug development to reduce postmenopausal adiposity.

scholarly journals Quantitative investigations of different vaccination policies for the control of congenital rubella syndrome (CRS) in the United Kingdom

1986 ◽  
Vol 96 (2) ◽  
pp. 305-333 ◽  
Author(s):  
R. M. Anderson ◽  
B. T. Grenfell
Keyword(s):  
Young Male ◽  
Parameter Estimates ◽  
Male And Female ◽  
Teenage Girls ◽  
Congenital Rubella ◽  
The United Kingdom ◽  
Age Related ◽  
Model Predictions ◽  
Female Children

SUMMARYThe paper examines predictions of the impact of various one-, two- and three-stage vaccination policies on the incidence of congenital rubella syndrome (CRS) in the United Kingdom with the aid of a mathematical model of the transmission dynamics of rubella virus. Parameter estimates for the model are derived from either serological data or case notifications, and special attention is given to the significance of age-related changes in the rate of exposure to rubella infection and heterogeneous mixing between age groups. Where possible, model predictions are compared with observed epidemiological trends.The principal conclusion of the analyses is that benefit is to be gained in the UK, both in the short and long term, by the introduction of a multiple-stage vaccination policy involving high levels of vaccination coverage of young male and female children (at around two years of age) and teenage girls (between the ages of 10–15 years), plus continued surveillance and vaccination of adult women in the child-bearing age classes. Model predictions suggest that to reduce the incidence of CRS in future years, below the level generated by a continuation of the current UK policy (the vaccination of teenage girls), would require high rates of vaccination > 60%) of both boys and girls at around two years of age. Numerical studies also suggest that uniform vaccination coverage levels of greater than 80–85% of young male and female children could, in the long term (40 years or more), eradicate rubella virus from the population. The robustness of these conclusions with respect to the accuracy of parameter estimates and various assumptions concerning the pattern of age-related change in exposure to infections and ‘who acquires infection from whom’ is discussed.

scholarly journals Sex Differences in Angiotensin II-Induced Hypertension and Kidney Injury: Role of AT1a Receptors in The Proximal Tubule of The Kidney

2021 ◽  
Author(s):  
Ana Paula Oliverio Leite ◽  
Xiao Chun Li ◽  
Ruman Hassan ◽  
Xiaowen Zheng ◽  
Barbara T Alexander ◽  
...  
Keyword(s):  
Sex Differences ◽  
Angiotensin Ii ◽  
Proximal Tubule ◽  
Kidney Injury ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Wild Type ◽  
Male And Female ◽  
Induced Hypertension ◽  
Different Strains

In the present study, we tested the hypothesis that there are significant sex differences in angiotensin II (Ang II)-induced hypertension and kidney injury using male and female wild-type and proximal tubule-specific AT1a receptor knockout mice (PT-Agtr1a-/-). Twelve groups (n=8-12 per group) of adult male and female wild-type and PT-Agtr1a-/- mice were infused with a pressor dose of Ang II via osmotic pump for 2 weeks (1.5 mg/kg/day, i.p.) and simultaneously treated with or without losartan (20 mg/kg/day, p.o.) to determine the respective roles of AT1a receptors in the proximal tubules versus systemic tissues. Basal systolic, diastolic, and mean arterial pressure were approximately 13 ± 3 mmHg lower (P<0.01), while basal 24 h urinary Na+, K+, and Cl- excretion were significantly higher in both male and female PT-Agtr1a-/- mice than wild-type controls (P<0.01) without significant sex differences between different strains. Both male and female wild-type and PT-Agtr1a-/- mice developed hypertension (P<0.01), and the magnitudes of the pressor responses to Ang II were similar between male and female wild-type and PT-Agtr1a-/- mice (n.s.). Likewise, Ang II-induced hypertension was significantly attenuated in both male and female PT-Agtr1a-/- mice (P<0.01). Furthermore, losartan attenuated the hypertensive responses to Ang II to similar extents in both male and female wild-type and PT-Agtr1a-/- mice. Finally, Ang II-induced kidney injury was attenuated in PT-Agtr1a-/- mice (P<0.01). In conclusion, the present study demonstrates that deletion of AT1a receptors in the proximal tubules of the kidney attenuates Ang II-induced hypertension and kidney injury without revealing significant sex differences.

scholarly journals Ageing Related Down-Regulation of Myocardial Connexin-43 and Up-Regulation of MMP-2 May Predict Propensity to Atrial Fibrillation in Experimental Animals

2016 ◽  
pp. S91-S100 ◽  
Author(s):  
V. NAGIBIN ◽  
T. EGAN BENOVA ◽  
C. VICZENCZOVA ◽  
B. SZEIFFOVA BACOVA ◽  
I. DOVINOVA ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Extracellular Matrix ◽  
Connexin 43 ◽  
Young Male ◽  
Matrix Metalloproteinase 2 ◽  
Down Regulation ◽  
Male And Female ◽  
Atrial Tissue ◽  
Age Related ◽  
Cx43 Mrna

Mechanisms underlying atrial fibrillation (AF), the most common cardiac arrhythmia, particularly in aged population, are not fully elucidated. We have previously shown an increased propensity of old guinea pigs (GPs) heart to inducible AF when comparing to young animals. This study aimed to verify our hypothesis that susceptibility of aged heart to AF may be attributed to abnormalities in myocardial connexin-43 (Cx43) and extracellular matrix that affect cardiac electrical properties. Experiments were conducted on male and female 4-week-old and 24-week-old GPs. Atrial tissue was processed for analysis of Cx43 topology using immunohistochemistry, expression of Cx43 protein using immunobloting, and expression of mRNA of Cx43 and extracellular matrix metalloproteinase-2 (MMP-2) using real time PCR. Immunohistochemistry revealed uniform Cx43 distribution predominantly on lateral sides of the cardiomyocytes of young male and female GP atria. In contrast, non-uniform distribution, mislocalization and reduced immunolabeling of Cx43 were detected in atria of old GPs. In parallel, the atrial tissue levels of Cx43 mRNA were significantly decreased, while mRNA expression of MMP-2 was significantly increased in old versus young GPs. The changes were more pronounced in old GPs males comparing to females. Findings indicate that age-related down-regulation of atrial Cx43 and up-regulation of MMP-2 as well as disordered Cx43 distribution can facilitate development of AF in old guinea pig hearts.

scholarly journals Uricase deficiency causes mild and multiple organ injuries in rats

PLoS ONE ◽  
2021 ◽  
Vol 16 (8) ◽  
pp. e0256594
Author(s):  
Nan Fan ◽  
Yun Yu ◽  
Lvyu Li ◽  
Heng Xia ◽  
Xiangxian Dong ◽  
...  
Keyword(s):  
Body Weight ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Weight Ratio ◽  
Young Male ◽  
Multiple Organ ◽  
Male Rats ◽  
Wild Type ◽  
Subsequent Increase ◽  
Wild Type Male

Uricase-deficient rats could be one of the optimal model animals to study hyperuricemia. The present study aimed to find the biological differences between uricase-deficient (Kunming-DY rats) and wild-type male rats. Uricase-deficient rats and wild-type rats were commonly bred. Their body weight, water and food consumption, 24-h urine and feces, uric acid in serum and organs, and serum indexes were recorded or assayed. Organs, including the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum, were examined using a routine hematoxylin-eosin staining assay. We found that the growth of male uricase-deficient rats was retarded. These rats excreted more urine than the wild-type rats. Their organ indexes (organ weight body weight ratio), of the heart, liver, kidney, and thymus significantly increased, while those of the stomach and small intestine significantly decreased. The uricase-deficient rats had a significantly higher level of serum uric acid and excreted more uric acid via urine at a higher concentration. Except for the liver, uric acid increased in organs and intestinal juice of uricase-deficient rats. Histological examination of the uricase-deficient rats showed mild injuries to the heart, liver, spleen, lung, kidney, thymus, stomach, duodenum, and ileum. Our results suggest that uricase-deficient rats have a different biological pattern from the wild-type rats. Uricase deficiency causes growth retardation of young male rats and the subsequent increase in serum uric acid results in mild organs injuries, especially in the kidney and liver.

scholarly journals Ostα−/−mice exhibit altered expression of intestinal lipid absorption genes, resistance to age-related weight gain, and modestly improved insulin sensitivity

2014 ◽  
Vol 306 (5) ◽  
pp. G425-G438 ◽  
Author(s):  
Sadie G. Wheeler ◽  
Christine L. Hammond ◽  
François R. Jornayvaz ◽  
Varman T. Samuel ◽  
Gerald I. Shulman ◽  
...  
Keyword(s):  
Weight Gain ◽  
Insulin Sensitivity ◽  
Bile Acids ◽  
Lipid Absorption ◽  
Acute Administration ◽  
Wild Type ◽  
Altered Expression ◽  
Male And Female ◽  
Fat Accumulation ◽  
Age Related

The organic solute transporter OSTα-OSTβ is a key transporter for the efflux of bile acids across the basolateral membrane of ileocytes and the subsequent return of bile acids to the liver. Ostα−/−mice exhibit reduced bile acid pools and impaired lipid absorption. In this study, wild-type and Ostα−/−mice were characterized at 5 and 12 mo of age. Ostα−/−mice were resistant to age-related weight gain, body fat accumulation, and liver and muscle lipid accumulation, and male Ostα−/−mice lived slightly longer than wild-type mice. Caloric intake and activity levels were similar for Ostα−/−and wild-type male mice. Fecal lipid excretion was increased in Ostα−/−mice, indicating that a defect in lipid absorption contributes to decreased fat accumulation. Analysis of genes involved in intestinal lipid absorption revealed changes consistent with decreased dietary lipid absorption in Ostα−/−animals. Hepatic expression of cholesterol synthetic genes was upregulated in Ostα−/−mice, showing that increased cholesterol synthesis partially compensated for reduced dietary cholesterol absorption. Glucose tolerance was improved in male Ostα−/−mice, and insulin sensitivity was improved in male and female Ostα−/−mice. Akt phosphorylation was measured in liver and muscle tissue from mice after acute administration of insulin. Insulin responses were significantly larger in male and female Ostα−/−than wild-type mice. These findings indicate that loss of OSTα-OSTβ protects against age-related weight gain and insulin resistance.

scholarly journals Fructose-Rich Diet Is a Risk Factor for Metabolic Syndrome, Proximal Tubule Injury and Urolithiasis in Rats

2021 ◽  
Vol 23 (1) ◽  
pp. 203
Author(s):  
Mariusz Flisiński ◽  
Andrzej Brymora ◽  
Natalia Skoczylas-Makowska ◽  
Anna Stefańska ◽  
Jacek Manitius
Keyword(s):  
Metabolic Syndrome ◽  
Uric Acid ◽  
Urinary Excretion ◽  
Proximal Tubule ◽  
Serum Insulin ◽  
Fractional Excretion ◽  
Urine Ph ◽  
Regular Diet ◽  
Male Wistar Rats ◽  
Excessive Consumption

Excessive consumption of fructose (FR) leads to obesity, metabolic syndrome (MS) and insulin resistance, which are known risk factors for kidney stones. The epidemiological study has suggested the association between fructose consumption and urolithiasis, but the precise mechanism is still not well understood. Male Wistar rats were assigned for 8 weeks to three groups with different FR content in diet: RD (n = 5)—regular diet with a FR < 3%; F10 (n = 6)—regular diet with an addition of 10% Fr in drinking water; F60 (n = 5)—60% FR as a solid food. Serum concentration of FR, creatinine (Cr), insulin (Ins), triglycerides (Tg), homocysteine (HCS), uric acid (UA), calcium (Ca), phosphate (Pi), magnesium (Mg) and sodium (Na) were measured. Based on 24 h urine collection the following tests were performed: urine pH, proteinuria (PCR), excretion of N-Acetyl-(D)-Glucosaminidase (NAG), monocyte chemoattractant protein (MCP-1), uric acid (uUAEx), phosphate (uPiEx), calcium (uCaEx), magnesium (uMgEx) and sodium (uNaEx). The creatinine clearance (CrCl) was calculated. Calcium deposits in kidney sections were examined using hematoxylin and eosin (HE) and von Kossa stains. The rats on F10 and F60, as compared to the RD diet, showed a tendency for lower CrCl, higher HCS level and some features of MS as higher Ins and TG levels. Interestingly, F10 (fluid) versus F60 (solid) diet led to higher serum Ins levels. F10 and F60 versus RD demonstrated higher urinary excretion of MCP-1 and NAG which were suggestive for inflammatory injury of the proximal tubule. F10 and F60 as compared to RD showed significantly lower uUAEx, although there were no differences in clearance and fractional excretion of UA. F60 versus RD induced severe phosphaturia (>30×) and natriuria (4×) and mild calciuria. F10 versus RD induced calciuria (3×), phosphaturia (2×) and mild natriuria. Calcium phosphate stones within the tubules and interstitium were found only in rats on FR diet, respectively, in two rats from the F10 group and another two in the F60 group. The rats which developed stones were characterized by significantly higher serum insulin concentration and urinary excretion of calcium and magnesium. A fructose-rich diet may promote development of calcium stones due to proximal tubule injury and metabolic syndrome.

Review of the Literature Examining the Association of Serum Uric Acid with Osteoporosis and Mechanistic Insights into Its Effect on Bone Metabolism

2019 ◽  
Vol 19 (3) ◽  
pp. 259-273 ◽  
Author(s):  
Neelam Kaushal ◽  
Divya Vohora ◽  
Rajinder K Jalali ◽  
Sujeet Jha
Keyword(s):  
Risk Factors ◽  
Bone Mineral Density ◽  
Uric Acid ◽  
Bone Metabolism ◽  
Serum Uric Acid ◽  
Bone Mineral ◽  
Molecular Mechanisms ◽  
Association Studies ◽  
Mineral Density ◽  
Age Related

Background And Objective:Osteoporosis is a common bone disorder that increases susceptibility to fragility bone fractures. The clinical and public health repercussions of osteoporosis are huge due to the morbidity, mortality, and cost of medical care linked with fragility fractures. Clinical assessment of osteoporotic risk factors can help to identify candidates at an early stage that will benefit from medical intervention and potentially lowering the morbidity and mortality seen with fractures and complications. Given this, research is ongoing to evaluate the association of osteoporosis with some novel or less well-studied risk factors/bio-markers such as uric acid (UA).Discussion:Uric acid’s antioxidant activity has been proposed to be one of the factors responsible for increasing longevity and lowering rates of age-related cancers during primate evolution, the level of which increased markedly due to loss of uricase enzyme activity (mutational silencing). Accumulated evidence shows that oxidative stress is the fundamental mechanism of age-related bone loss and acts via enhancing osteoclastic activity and increasing bone resorption. Antioxidant substances such as ascorbic acid scavenge free radicals are positively related to bone health. Thus, it is hypothesized that uric acid holds bone-protective potential owing to its potent antioxidative property. Several correlation studies have been conducted globally to investigate the relationship between serum uric acid with bone mineral density and osteoporosis. Few pre-clinical studies have tried to investigate the interaction between uric acid and bone mineral density and reported important role played via Runt-related transcription factor 2 (RUNX2)/core-binding factor subunit alpha-1 (CBF-alpha-1), Wingless-related integration site (Wnt)-3a/β-catenin signaling pathway and 11β Hydroxysteroid Dehydrogenase type 1.Conclusion:In this review, the authors provided a comprehensive summary of the literature related to association studies reported in humans as well work done until date to understand the potential cellular and molecular mechanisms that interplay between uric acid and bone metabolism.

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