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Salt Sensitivity (salt + sensitivity)
Selected AbstractsSalt-Sensitive Hypertension Resulting From Nitric Oxide Synthase Inhibition is Associated with Loss of Regulation of Angiotensin II in the RatEXPERIMENTAL PHYSIOLOGY, Issue 1 2002G. Hodge In the Dahl salt-sensitive hypertensive rat, a diet containing L-arginine, the natural substrate for nitric oxide synthase, abrogates the hypertension. We postulated that nitric oxide synthase inhibition might induce a salt-sensitive form of hypertension and that this salt sensitivity might be linked to a loss of the regulatory effect of sodium ingestion on angiotensin II (Ang II) and angiotensinogen. Male Wistar-Kyoto rats were randomised to a diet containing 0.008%, 2.2% or 4.4% sodium chloride and to treatment with the NO synthase inhibitor L-NAME (10 mg kg,1 day,1) in the drinking water, or drinking water alone (Controls) for 4 weeks. Blood pressure was measured by tail cuff plethysmography twice weekly. After 4 weeks, the rats were anaesthetised and truncal blood collected for determination of angiotensinogen, renin, angiotensin I (Ang I), Ang II and aldosterone concentrations as well as angiotensin-converting enzyme (ACE) activity. Systolic blood pressure increased with increasing dietary sodium intake in the L-NAME-treated rats (P < 0.05). Plasma renin and aldosterone concentrations decreased with increasing dietary sodium intake in both Control and L-NAME-treated rats. Ang I and ACE activity were unchanged by increasing dietary sodium intake. In contrast, the plasma concentration of Ang II and angiotensinogen increased with increasing dietary sodium (P < 0.05 and P < 0.005, respectively). Treatment with the Ang II receptor blocker, losartan, reversed the blood pressure increase. We conclude that treatment with L-NAME induces an increase in blood pressure that is at least in part salt sensitive. Further, the salt-sensitive component appears to be Ang II-dependent, as it was associated with increasing plasma Ang II levels and could be reversed by treatment with an Ang II receptor antagonist. [source] Salt-resistant homodimeric bactenecin, a cathelicidin-derived antimicrobial peptideFEBS JOURNAL, Issue 15 2008Ju Y. Lee The cathelicidin antimicrobial peptide bactenecin is a ,-hairpin molecule with a single disulfide bond and broad antimicrobial activity. The proform of bactenecin exists as a dimer, however, and it has been proposed that bactenecin is released as a dimer in vivo, although there has been little study of the dimeric form of bactenecin. To investigate the effect of bactenecin dimerization on its biological activity, we characterized the dimer's effect on phospholipid membranes, the kinetics of its bactericidal activity, and its salt sensitivity. We initially synthesized two bactenecin dimers (antiparallel and parallel) and two monomers (,-hairpin and linear). Under oxidative folding conditions, reduced linear bactenecin preferentially folded into a dimer forming a ladder-like structure via intermolecular disulfide bonding. As compared to the monomer, the dimer had a greater ability to induce lysis of lipid bilayers and was more rapidly bactericidal. Interestingly, the dimer retained antimicrobial activity at physiological salt concentrations (150 mm NaCl), although the monomer was inactivated. This salt resistance was also seen with bactenecin dimer containing one intermolecular disulfide bond, and the bactenecin dimer appears to undergo multimeric oligomerization at high salt concentrations. Overall, dimeric bactenecin shows potent and rapid antimicrobial activity, and resists salt-induced inactivation under physiological conditions through condensation and oligomerization. These characteristics shed light on the features that a peptide would need to serve as an effective therapeutic agent. [source] ISC1-encoded inositol phosphosphingolipid phospholipase C is involved in Na+/Li+ halotolerance of Saccharomyces cerevisiaeFEBS JOURNAL, Issue 16 2002Christian Betz In Saccharomyces cerevisiae, toxic concentrations of Na+ orLi+ ions induce the expression of the cation-extrusion ATPase gene, ENA1. Several well-studied signal transduction pathways are known correlating high salinity to the transcriptional activation of ENA1. Nevertheless, information on the actual sensing mechanism initiating these pathways is limited. Here, we report that the ISC1 -encoded phosphosphingolipid-specific phospholipase C appears to be involved in stimulation of ENA1 expression and, consequently, in mediating Na+ and Li+ tolerance in yeast. Deletion of ISC1 distinctly decreased cellular Na+ and Li+ tolerance as growth of the ,isc1::HIS5 mutant, DZY1, was severely impaired by 0.5 m NaCl or 0.01 m LiCl. In contrast,K+ tolerance and general osmostress regulation wereunaffected. Isc1, mutant growth with 0.9 m KCl and glycerol accumulation in the presence of 0.9 m NaCl or 1.5 m sorbitol were comparable to that of the wild-type. ENA1 -lacZ reporter studies suggested that the increased salt sensitivity of the isc1, mutant is related to a significant reduction of Na+/Li+ -stimulated ENA1 expression. Correspondingly, Ena1p-dependent extrusion of Na+/Li+ ions was less efficient in the isc1, mutant than in wild-type cells. Itis suggested that ISC1 -dependent hydrolysis of an unidentified yeast inositol phosphosphingolipid represents an early event in one of the salt-induced signalling pathways of ENA1 transcriptional activation. [source] A respiratory-deficient mutation associated with high salt sensitivity in Kluyveromyces lactisFEMS YEAST RESEARCH, Issue 2 2007Paola Goffrini Abstract A salt-sensitive mutant of Kluyveromyces lactis was isolated that was unable to grow in high-salt media. This mutant was also respiratory-deficient and temperature-sensitive for growth. The mutation mapped in a single nuclear gene that is the ortholog of BCS1 of Saccharomyces cerevisiae. The BCS1 product is a mitochondrial protein required for the assembly of respiratory complex III. The bcs1 mutation of S. cerevisiae leads to a loss of respiration, but, unlike in K. lactis, it is not accompanied by salt sensitivity. All the respiratory-deficient K. lactis mutants tested were found to be salt-sensitive compared to their isogenic wild-type strains. In the presence of the respiratory inhibitor antimycin A, the wild-type strain also became salt-sensitive. By contrast, none of the S. cerevisiae respiratory-deficient mutants tested showed increased salt sensitivity. The salt sensitivity of the Klbcs1 mutant, but not its respiratory deficiency, was suppressed by the multicopy KlVMA13 gene, a homolog of the S. cerevisiae VMA13 gene encoding a subunit of the vacuolar H+ -ATPase. These results suggest that cellular salt homeostasis in K. lactis is strongly dependent on mitochondrial respiratory activity, and/or that the ion homeostasis of mitochondria themselves could be a primary target of salt stress. [source] Therapeutic Lifestyle Changes for Hypertension and Cardiovascular Risk ReductionJOURNAL OF CLINICAL HYPERTENSION, Issue 1 2003Karol Watson MD Elevated blood pressure is the most common chronic illness in the United States, affecting more than 50 million people. Hypertension is an even greater problem in the African American community. Traditionally, management of hypertension and cardiovascular risk reduction has focused on drug therapy; however, several studies have shown the benefits of therapeutic lifestyle changes for blood pressure lowering and cardiovascular risk reduction. Therapeutic lifestyle changes to reduce blood pressure have enormous potential as a means for preventing and controlling hypertension and thereby reducing the risk of coronary heart disease. Although the reductions in blood pressure are relatively modest with these approaches, they could potentially have a beneficial impact on overall cardiovascular morbidity and mortality when applied to the whole population. Because of their high prevalence of certain cardiovascular risk factors (e.g., obesity, diabetes mellitus) and greater salt sensitivity, therapeutic lifestyle changes have particular relevance for African Americans. [source] A membrane-bound FtsH protease is involved in osmoregulation in Synechocystis sp.MOLECULAR MICROBIOLOGY, Issue 1 2007PCC 6803: the compatible solute synthesizing enzyme GgpS is one of the targets for proteolysis Summary Protein quality control and proteolysis are involved in cell maintenance and environmental acclimatization in bacteria and eukaryotes. The AAA protease FtsH2 of the cyanobacterium Synechocystis sp. PCC 6803 was identified during a screening for mutants impaired in osmoregulation. The ftsH2, mutant was salt sensitive because of a decreased level of the osmoprotectant glucosylglycerol (GG). In spite of wild type-like transcription of the ggpS gene in ftsH2, cells the GgpS protein content increased but only low levels of GgpS activity were observed. Consequently, salt tolerance of the ftsH2, mutant decreased while addition of external osmolyte complemented the salt sensitivity. The proteolytic degradation of the GgpS protein by FtsH2 was demonstrated by an in vitro assay using inverted membrane vesicles. The GgpS is part of a GG synthesizing complex, because yeast two-hybrid screens identified a close interaction with the GG-phosphate phosphatase. Besides GgpS as the first soluble substrate of a cyanobacterial FtsH protease, several other putative targets were identified by a proteomic approach. We present a novel molecular explanation for the salt-sensitive phenotype of bacterial ftsH, mutants as the result of accumulation of inactive enzymes for compatible solute synthesis, in this case GgpS the key enzyme of GG synthesis. [source] The Na+ transporter AtHKT1;1 controls retrieval of Na+ from the xylem in ArabidopsisPLANT CELL & ENVIRONMENT, Issue 4 2007ROMOLA JANE DAVENPORT ABSTRACT HKT-type transporters appear to play key roles in Na+ accumulation and salt sensitivity in plants. In Arabidopsis HKT1;1 has been proposed to influx Na+ into roots, recirculate Na+ in the phloem and control root : shoot allocation of Na+. We tested these hypotheses using 22Na+ flux measurements and ion accumulation assays in an hkt1;1 mutant and demonstrated that AtHKT1;1 contributes to the control of both root accumulation of Na+ and retrieval of Na+ from the xylem, but is not involved in root influx or recirculation in the phloem. Mathematical modelling indicated that the effects of the hkt1;1 mutation on root accumulation and xylem retrieval were independent. Although AtHKT1;1 has been implicated in regulation of K+ transport and the hkt1;1 mutant showed altered net K+ accumulation, 86Rb+ uptake was unaffected by the hkt1;1 mutation. The hkt1;1 mutation has been shown previously to rescue growth of the sos1 mutant on low K+; however, HKT1;1 knockout did not alter K+ or 86Rb+ accumulation in sos1. [source] Distance dependence and salt sensitivity of pairwise, coulombic interactions in a proteinPROTEIN SCIENCE, Issue 5 2002Kelly K. Lee Abstract Histidine pKa values were measured in charge-reversal (K78E, K97E, K127E, and K97E/K127E) and charge-neutralization (E10A, E101A, and R35A) mutants of staphylococcal nuclease (SNase) by 1H-NMR spectroscopy. Energies of interaction between pairs of charges (,Gij) were obtained from the shifts in pKa values relative to wild-type values. The data describe the distance dependence and salt sensitivity of pairwise coulombic interactions. Calculations with a continuum electrostatics method captured the experimental ,Gij when static structures were used and when the protein interior was treated empirically with a dielectric constant of 20. The ,Gij when rij , 10 Å were exaggerated slightly in the calculations. Coulomb's law with a dielectric constant near 80 and a Debye-Hückel term to account for screening by the ionic strength reproduced the salt sensitivity and distance dependence of ,Gij as well as the structure-based method. In their interactions with each other, surface charges behave as if immersed in water; the Debye length describes realistically the distance where interactions become negligible at a given ionic strength. On average, charges separated by distances (rij) ,5 Å interacted with ,Gij , 0.6 kcal/mole in 0.01 M KCl, but ,Gij decayed to ,0.10 kcal/mole when rij = 20 Å. In 0.10 M KCl, ,Gij , 0.10 kcal/mole when rij = 10 Å. In 1.5 M KCl, only short-range interactions with rij , 5 Å persisted. Although at physiological ionic strengths the interactions between charges separated by more than 10 Å are extremely weak, in situations where charge imbalance exists many weak interactions can cumulatively produce substantial effects. [source] | |||||||||||||