scholarly journals FXYD proteins and sodium pump regulatory mechanisms

2021 ◽  
Vol 153 (4) ◽  
Author(s):  
John Q. Yap ◽  
Jaroslava Seflova ◽  
Ryan Sweazey ◽  
Pablo Artigas ◽  
Seth L. Robia
Keyword(s):  
Posttranslational Modifications ◽  
Protein Trafficking ◽  
Regulatory Mechanisms ◽  
Structural Determinants ◽  
Sodium Potassium ◽  
Transmembrane Peptides ◽  
Biophysical Studies ◽  
Clinical Correlations ◽  
Sodium And Potassium ◽  
Physiological Systems

The sodium/potassium-ATPase (NKA) is the enzyme that establishes gradients of sodium and potassium across the plasma membrane. NKA activity is tightly regulated for different physiological contexts through interactions with single-span transmembrane peptides, the FXYD proteins. This diverse family of regulators has in common a domain containing a Phe-X-Tyr-Asp (FXYD) motif, two conserved glycines, and one serine residue. In humans, there are seven tissue-specific FXYD proteins that differentially modulate NKA kinetics as appropriate for each system, providing dynamic responsiveness to changing physiological conditions. Our understanding of how FXYD proteins contribute to homeostasis has benefitted from recent advances described in this review: biochemical and biophysical studies have provided insight into regulatory mechanisms, genetic models have uncovered remarkable complexity of FXYD function in integrated physiological systems, new posttranslational modifications have been identified, high-resolution structural studies have revealed new details of the regulatory interaction with NKA, and new clinical correlations have been uncovered. In this review, we address the structural determinants of diverse FXYD functions and the special roles of FXYDs in various physiological systems. We also discuss the possible roles of FXYDs in protein trafficking and regulation of non-NKA targets.

scholarly journals Changes in the Membrane Permeability of Frog's Sartorius Muscle Fibers in Ca-Free EDTA Solution

1963 ◽  
Vol 47 (2) ◽  
pp. 379-392 ◽  
Author(s):  
H. Kimizuka ◽  
K. Koketsu
Keyword(s):  
Membrane Permeability ◽  
Chloride Content ◽  
Chloride Ions ◽  
Sartorius Muscle ◽  
Constant Field ◽  
Sodium Influx ◽  
Sodium Potassium ◽  
Edta Solution ◽  
Frog Sartorius ◽  
Sodium And Potassium

The changes in the membrane permeability to sodium, potassium, and chloride ions as well as the changes in the intracellular concentration of these ions were studied on frog sartorius muscles in Ca-free EDTA solution. It was found that the rate constants for potassium and chloride efflux became almost constant within 10 minutes in the absence of external calcium ions, that for potassium increasing to 1.5 to 2 times normal and that for chloride decreasing about one-half. The sodium influx in Ca-free EDTA solution, between 30 and 40 minutes, was about 4 times that in Ringer's solution. The intracellular sodium and potassium contents did not change appreciably but the intracellular chloride content had increased to about 4 times normal after 40 minutes. By applying the constant field theory to these results, it was concluded that (a) PCl did not change appreciably whereas PK decreased to a level that, in the interval between 10 and 40 minutes, was about one-half normal, (b) PNa increased until between 30 and 40 minutes it was about 8 times normal. The low value of the membrane potential between 30 and 40 minutes was explained in terms of the changes in the membrane permeability and the intracellular ion concentrations. The mechanism for membrane depolarization in this solution was briefly discussed.

scholarly journals Postprenylation CAAX Processing Is Required for Proper Localization of Ras but Not Rho GTPases

2005 ◽  
Vol 16 (4) ◽  
pp. 1606-1616 ◽  
Author(s):  
David Michaelson ◽  
Wasif Ali ◽  
Vi K. Chiu ◽  
Martin Bergo ◽  
Joseph Silletti ◽  
...  
Keyword(s):  
Posttranslational Modifications ◽  
Protein Trafficking ◽  
Rho Gtpases ◽  
Ras Proteins ◽  
Rho Proteins ◽  
Carboxyl Methylation ◽  
C Terminus ◽  
Individual Contributions ◽  
The Individual ◽  
And Function

The CAAX motif at the C terminus of most monomeric GTPases is required for membrane targeting because it signals for a series of three posttranslational modifications that include isoprenylation, endoproteolytic release of the C-terminal– AAX amino acids, and carboxyl methylation of the newly exposed isoprenylcysteine. The individual contributions of these modifications to protein trafficking and function are unknown. To address this issue, we performed a series of experiments with mouse embryonic fibroblasts (MEFs) lacking Rce1 (responsible for removal of the –AAX sequence) or Icmt (responsible for carboxyl methylation of the isoprenylcysteine). In MEFs lacking Rce1 or Icmt, farnesylated Ras proteins were mislocalized. In contrast, the intracellular localizations of geranylgeranylated Rho GTPases were not perturbed. Consistent with the latter finding, RhoGDI binding and actin remodeling were normal in Rce1- and Icmt-deficient cells. Swapping geranylgeranylation for farnesylation on Ras proteins or vice versa on Rho proteins reversed the differential sensitivities to Rce1 and Icmt deficiency. These results suggest that postprenylation CAAX processing is required for proper localization of farnesylated Ras but not geranygeranylated Rho proteins.

scholarly journals Regulatory mechanisms of phosphatase of regenerating liver (PRL)-3

2016 ◽  
Vol 44 (5) ◽  
pp. 1305-1312 ◽  
Author(s):  
Teresa Rubio ◽  
Maja Köhn
Keyword(s):  
Drug Development ◽  
Posttranslational Modifications ◽  
Human Cancer ◽  
Regulatory Mechanisms ◽  
Therapeutic Drug ◽  
Regenerating Liver ◽  
Cancer Types ◽  
Tumor Metastases ◽  
Phosphatase Of Regenerating Liver ◽  
Incomplete Picture

The phosphatase of regenerating liver (PRL)-3 is overexpressed in many human cancer types and tumor metastases when compared with healthy tissues. Different pathways and mechanisms have been suggested to modulate PRL-3 expression levels and activity, giving some valuable insights but still leaving an incomplete picture. Investigating these mechanisms could provide new targets for therapeutic drug development. Here, we present an updated overview and summarize recent findings concerning the different PRL-3 expression regulatory mechanisms and posttranslational modifications suggested to modulate the activity, localization, or stability of this phosphatase.

Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats

1993 ◽  
Vol 74 (6) ◽  
pp. 2795-2800 ◽  
Author(s):  
R. Behm ◽  
H. Mewes ◽  
W. H. DeMuinck Keizer ◽  
T. Unger ◽  
R. Rettig
Keyword(s):  
Carotid Body ◽  
Normobaric Hypoxia ◽  
Sodium Potassium ◽  
Water Excretion ◽  
Excretory Function ◽  
Arterial Blood ◽  
Peripheral Arterial ◽  
Renal Responses ◽  
Arterial Po2 ◽  
Sodium And Potassium

The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.

Effects of Synthetic Atrial Natriuretic Peptides on Sodium-Potassium Transport in Human Erythrocytes

1985 ◽  
Vol 69 (2) ◽  
pp. 223-226 ◽  
Author(s):  
G. A. Sagnella ◽  
D. A. Nolan ◽  
A. C. Shore ◽  
G. A. MacGregor
Keyword(s):  
Loop Diuretic ◽  
Sodium Pump ◽  
Human Erythrocytes ◽  
Atrial Natriuretic Peptides ◽  
Sodium Potassium ◽  
Potassium Ion Transport ◽  
Wide Range ◽  
Natriuretic Effect ◽  
Cotransport System ◽  
Sodium And Potassium

1. The effects of synthetic human and rat atrial peptides on sodium and potassium ion transport has been investigated in intact human erythrocytes. 2. The effects of these peptides have been tested on the active, sodium pump-dependent (ouabain-sensitive) and on the sodium-potassium cotransport system (bumetanide-sensitive) with 86Rb used as a tracer. 3. Human (α-ANP, 28 amino acids) or rat (atriopeptin III) atrial peptides, over a wide range of concentrations, did not influence the uptake of 86Rb in either the ouabain-sensitive or the bumetanide-sensitive transport system. 4. These results suggest that the natriuretic effect of the atrial peptides is not mediated through inhibition of the sodium pump or the loop-diuretic-sensitive Na-K cotransport.

Abstract P053: Sodium and Potassium Intake and Blood Pressure and Risk of Hypertension Among U.S. Adults - Results From NHANES 2003-2008

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Zefeng Zhang ◽  
Mary Cogswell ◽  
Cathleen Gillespie ◽  
Jing Fang ◽  
Shifan Dai ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Sodium Potassium ◽  
Potassium Intake ◽  
Undiagnosed Hypertension ◽  
Unit Increase ◽  
Nationally Representative ◽  
Prevention Of Hypertension ◽  
Sodium And Potassium

Introduction: Evidence from randomized controlled trials demonstrates higher sodium and/or lower potassium intake increase blood pressure and the risk of hypertension. However, the relationship between sodium, potassium and blood pressure has not been examined using nationally representative sample and estimated usual intakes of these nutrients. Hypothesis: We hypothesized that usual sodium and potassium intake have opposing effects on blood pressure and a higher sodium-to-potassium ratio is associated with elevated blood pressure and hypertension. Methods: We analyzed data on 12,854 participants aged 20 years and older from the 2003-2008 National Health and Nutrition Examination Surveys. We estimated the usual intakes of sodium and potassium from the diet accounting for measurement error. Mean blood pressure was calculated from up to three readings on each subject and hypertension included both diagnosed and undiagnosed hypertension. We used multivariable linear regression to examine the associations between intakes of sodium, potassium and their ratio with systolic and diastolic blood pressure, and logistic regression for associations with hypertension. Results: The average estimated usual intakes of sodium and potassium were 3465 and 2741 mg/d, respectively. The average sodium-to-potassium ratio was 1.39; higher ratios were observed among males, younger and non-Hispanic black participants. After adjustment for potential confounders, usual intakes of sodium, potassium and their ratio were significantly associated with systolic blood pressure, with an increase of 1.08 mm Hg (95% confidence interval (CI): 0.30 – 1.86) and a decrease of 1.47 mmHg (95% CI: -2.31, -0.63) for every 1000 mg/d increase in sodium and potassium intake, respectively, and an increase of 2.80 mmHg (95% CI: 0.90 - 4.70) for every unit increase in sodium-to-potassium ratio. No association was found for diastolic blood pressure. The adjusted odds ratio (OR) comparing the highest and lowest quartiles of usual sodium or potassium intakes were 1.63 (95% CI: 1.14 - 2.34) and 0.61 (95% CI: 0.45 - 0.82), respectively, for risk of hypertension. For sodium-to-potassium ratio, the adjusted OR was 1.49 (95% CI: 1.17 - 1.89). The patterns of association were largely consistent across age, gender, race/ethnicity, body mass index, and education subgroups. Conclusions: In conclusion, our results indicated higher sodium and lower potassium intakes were associated with increased systolic blood pressure and risk for hypertension. The combined effect of sodium and potassium might play a central role in the pathogenesis of hypertension. The results further confirm that reducing sodium and increasing potassium intakes concurrently may have important implications in the prevention of hypertension, and hence, of cardiovascular disease.

Constituents of Bull Seminal Plasma

1954 ◽  
Vol 31 (4) ◽  
pp. 561-572
Author(s):  
LORD ROTHSCHILD ◽  
H. BARNES
Keyword(s):  
Seminal Plasma ◽  
Freezing Point ◽  
Average Concentration ◽  
Alternative Methods ◽  
Strongly Correlated ◽  
Sodium Potassium ◽  
Total N ◽  
Electrometric Titration ◽  
Sodium And Potassium ◽  
Total P

1. The concentrations of the main inorganic and certain organic constituents of bull seminal plasma have been examined. The average concentrations, in mg./100 ml., were: Sodium 258 Chloride 175 Potassium 172 Citrate 620 Calcium 37 Fructose 460 Magnesium 8 Total N 877 Iron 2 Total P 57 2. Sodium and potassium were found to be inversely correlated, r= -0.86, p<0.001. 3. Calcium, chloride, fructose, citrate and total nitrogen were also strongly correlated (p<0.001), in such a way that a knowledge of the concentration of any one of the constituents enabled the average concentration of the other four in the sample to be predicted with considerable accuracy. 4. Sodium, potassium and chloride were estimated by standard chemical methods and with the flame photometer (sodium and potassium) and by electrometric titration (chloride). The applicability of the alternative methods of estimation, which require very small quantities of seminal plasma, has been examined and is discussed. 5. The freezing-point depression, Δ, of bull seminal plasma was -0.533, standard error of mean, 0.005. 6. The Δ's of a number of laboratory and field diluents were also examined; with two exceptions they were found to vary markedly from Δ for bull seminal plasma.

Dietary Sodium, Potassium, and Sodium to Potassium Ratio in Patients With Systemic Lupus Erythematosus

2022 ◽  
pp. 109980042110654
Author(s):  
María Correa-Rodríguez ◽  
Sara DelOlmo-Romero ◽  
Gabriela Pocovi-Gerardino ◽  
José-Luis Callejas-Rubio ◽  
Raquel Ríos-Fernández ◽  
...  
Keyword(s):  
Disease Activity ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Complement C3 ◽  
Systemic Lupus ◽  
Sodium Potassium ◽  
Complement C4 ◽  
Potassium Intake ◽  
Dietary Potassium ◽  
Sodium And Potassium

Purpose: The aim of this study was to investigate the association between dietary sodium, potassium, and sodium:potassium ratio and clinical disease activity parameters, damage accrual, and cardiovascular disease risk factors in a population of patients with systemic lupus erythematous (SLE). Research design and study sample: A cross-sectional study including a total of 280 patients was conducted (90.4% females; mean age 46.9 ± 12.85 years). Data collection: The SLE Disease Activity Index (SLEDAI-2K) and the SDI Damage Index were used to assess disease activity and disease-related damage, respectively. A 24-hour diet recall was used to estimate dietary intake of sodium and potassium. Results: Dietary sodium intake was significantly associated with anti-dsDNA ( β  =  −.005; 95% CI [.002 .008]; p = .001) and complement C4 level ( β  =  −.002; 95% CI [−.003, .000]; p = .039). Dietary potassium intake was also significantly associated with complement C3 level ( β  =  −.004; 95% CI [−.007, −.001]; p = .021). Multiple logistic regression models revealed a positive association between dietary sodium intake and the risk of having hsCRP > 3 ( p = .005) and an inverse association between dietary potassium intake and the risk of having hsCRP > 3 ( p = .004). Conclusions: SLE patients with higher dietary sodium and lower dietary potassium intakes had an increased risk of higher hsCRP. Dietary sodium intake was significantly associated with anti-dsDNA and complement C4 level, while dietary potassium intake was associated with complement C3 level, supporting that dietary sodium and potassium intakes might play a key role in markers related to disease activity in SLE patients.

Electrolytes

2012 ◽  
Author(s):  
Matthew R Rosengart
Keyword(s):  
Systematic Approach ◽  
Cell Function ◽  
Patient Survival ◽  
Regulatory Mechanisms ◽  
Electrolyte Disorders ◽  
Sodium Potassium ◽  
Electrolyte Homeostasis ◽  
Total Body ◽  
Additional Support ◽  
Underlying Pathophysiology

Cell function and thus life depend on the preservation of several electrochemical gradients. Evolutionary pressures have developed several regulatory mechanisms, the penultimate goal of which is to maintain total body and distribution of each electrolyte within the intracellular and extracellular compartments at concentrations compatible with life. Ultimately, patient survival depends on this balance despite the continual changes imposed by both internal physiologic processes and external stressors. During periods of critical illness, however, these mechanisms can be overwhelmed, necessitating additional support. Indeed, disorders of electrolyte homeostasis are highly prevalent among intensive care unit patients, and severe disturbances are associated with elevated mortality. As has been previously learned, merely normalizing laboratory abnormalities without addressing the underlying pathophysiology does little to improve outcome. Thus, for those providing this care, an in-depth understanding of the biochemistry and physiology of electrolyte disorders and a systematic approach to diagnosis and therapy are complementary components essential for patient survival. This chapter discusses the major electrolytes—sodium, potassium, calcium and phosphate, and magnesium—and covers the hyper- and hypodeficiencies and disturbances for each electrolyte. This review contains 7 Figures, 6 Tables, 5 Etiologic Algorithms, and 106 References.

Bone resorption and mineral excretion in rats during spaceflight

1983 ◽  
Vol 244 (3) ◽  
pp. R327-R331 ◽  
Author(s):  
C. E. Cann ◽  
R. R. Adachi
Keyword(s):  
Neutron Activation Analysis ◽  
Bone Resorption ◽  
Time Course ◽  
Large Change ◽  
Sodium Potassium ◽  
Total Body Calcium ◽  
Mineral Excretion ◽  
Synchronous Control ◽  
Total Body ◽  
Sodium And Potassium

Bone resorption was measured directly in flight and synchronous control rats during COSMOS 1129. Continuous tracer administration techniques were used, with replacement of dietary calcium with isotopically enriched 40Ca and measurement by neutron activation analysis of the 48Ca released by the skeleton. There is no large change in bone resorption in rats at the end of 20 days of spaceflight as has been found for bone formation. Based on the time course of changes, the measured 20–25% decrease in resorption is probably secondary to a decrease in total body calcium turnover. The excretion of sodium, potassium, and zinc all increase during flight, sodium and potassium to a level four to five times control values.

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