Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A short treatment of dog renal brush-border membrane vesicles (BBMV) with sodium cholate, followed by dialysis of the detergent, reorients the polarity of H(+)-ATPase in the membrane and exposes its ATP binding sites to the extravesicular space, as previously shown with pig BBMV. In cholate-pretreated vesicles, the H(+)-ATPase remains fully active, but is inserted under the reversed polarity in sealed vesicles. A large spontaneous N-ethylmaleimide-sensitive ATPase activity is thus observed, as well as a steep intravesicular acidification upon external ATP addition, two findings absent in native vesicles. The ability of nitrate plus ATP to dissociate the hydrolytic subunits ot the proton pump in cholate-pretreated vesicles, but not in native vesicles, demonstrates that most of the ATP binding subunits are accessible to ATP following cholate treatment. The sensitivity of the cytoplasmic domain of the H(+)-ATP activity to trypsin also confirms the reorientation of the enzyme in cholate-pretreated vesicles. The H(+)-ATPase and alkaline phosphatase remain largely associated with the membranes after the treatment with cholate, but gamma-glutamyltranspeptidase, aminopeptidase N, and neutral endopeptidase are largely solubilized. Upon dialysis of cholate, all these enzymes are in part reinserted in the membrane according to their original polarity. The reorientation process is however specific for the H(+)-ATPase. Cholate treatment does not increase the formation of inside-out vesicles. Thus the treatment with cholate really reorients the polarity of the H(+)-ATPase in vesicles and allows for study of the proton pumping capacity of vacuolar H(+)-ATPase of proximal tubules.
 ...
PMID:Effect of cholate on H(+)-ATPase and other proteins of dog renal brush-border membrane. 812 55

The major proteinase in maize (Zea mays) roots behaves as a serine endopeptidase. A possible physiological role of this enzyme could be in the turnover of nitrate reductase (NR) and, as such, it could be of great importance in regulating the assimilation of nitrate. The objective of this research was to elucidate the specificity and uniqueness of maize root proteinase. When bovine serum albumin and an NR purified from Chlorella vulgaris were used as substrates, the maize root proteinase exhibited a preference for cleavages such that the amino acid on the amino side of the scissile bond was alanine. This information was established by microsequence analysis of the N termini of proteolytic fragments, and carboxypeptidase Y analysis of the C termini of proteolytic fragments of substrates hydrolyzed by the proteinase. Cleavage occurred at the sequence Ala/Ala-Ala-Ala-Pro-Glu in Chlorella NR, and at the sequence Ala-Asp-Glu-Ser-His-Ala-Gln in bovine serum albumin. When bovine serum albumin was the substrate, the maize root proteinase yielded a peptide map that is unique relative to those created with the other serine endopeptidases elastase, trypsin, or chymotrypsin. Based on our data, the maize root proteinase appears to cleave peptide bonds at the carboxy side of alanine. Because of its specificity, it should have useful applications in protein chemistry.
 ...
PMID:Characterization of a maize root proteinase. 827 5

Endothelin, a potent vasoactive peptide originally isolated from cultured porcine endothelial cells, (1) elicits hemodynamic and glycogenolytic actions in perfused rat liver; (2) evokes phosphoinositide signaling in hepatic cells; and (3) stimulates synthesis of mediators in Kupffer cells and glucose production in hepatocytes. Recently, we characterized receptor(s) for endothelin on hepatocytes (C. R. Gandhi, R. H. Behal, S. A. K. Harvey, T. Nouchi, and M. S. Olson, Biochem. J. 287, 897-904, 1992). Both hepatocytes and Kupffer cells rapidly internalize [125I]endothelin-1 ([125I]ET-1). In the present study we exposed primary cultures of hepatocytes or Kupffer cells to [125I]ET-1 and analyzed the radiolabeled metabolites which appeared in the cell medium. Six metabolites were separated by high-performance liquid chromatography (HPLC) from hepatocyte medium; these peaks had approximate elution times of 5 (free iodide), 22, 35, 37, 38, and 41 min, respectively, whereas the elution time for [125I]ET-1 was 43 min. The kinetics of formation of the metabolites, and experiments using excess unlabeled ET-1, both showed that internalization of the native peptide by hepatocytes is required for the metabolism of [125I]ET-1 into metabolite, and for the subsequent deiodination of metabolite. The formation of metabolites does not require internalization of the native peptide. In Kupffer cells, the cell medium contained only metabolite and metabolite. Internalization of the native peptide was required for the formation of metabolite but not for metabolite. Three classes of [125I]ET-1 metabolites from hepatic cells also were separated by sequential precipitation with trichloroacetic acid (TCA) and with silver nitrate. This procedure facilitated multiple rapid assays of [125I]ET-1 metabolism. Phosphoramidon, an inhibitor of neutral metalloendopeptidases, did not affect significantly the binding or the metabolism of [125I]ET-1 by hepatocytes or Kupffer cells. The aminopeptidase inhibitor bacitracin strongly attenuated [125I]ET-1 metabolism by hepatocytes, with a concomitant increase in the intracellular content of [125I]ET-1. These data suggest that enzymes capable of endothelin degradation are present both on the surface and in the intracellular compartment of hepatic cells, and that endothelin is not metabolized by neutral endopeptidase 24.11 in the liver.
 ...
PMID:Hepatic effects of endothelin: metabolism of [125I]endothelin-1 by liver-derived cells. 834 54

The aim of the present study was to investigate some putative neurotransmitters involved in nociception and pain in parturients during active labour experiencing intense visceral pain. The concentration of the excitatory amino acid aspartate was significantly increased, and there was a tendency for an increase in glutamate, in lumbar cerebrospinal fluid (CSF) of parturients in active vaginal labour compared with control patients without pain subjected to elective caesarean section. The CSF concentration of the nitric oxide breakdown product nitrate was significantly decreased in parturients compared with control patients and healthy volunteers. No significant differences in the concentrations of substance P, substance P-endopeptidase or met-enkephalin were detected between parturients and controls. Our data suggest a paradoxical negative relationship between CSF concentrations of excitatory amino acids and nitric oxide in labour pain. The mechanisms behind this finding is unclear at present.
 ...
PMID:Increased cerebrospinal fluid concentration of aspartate but decreased concentration of nitric oxide breakdown products in women experiencing visceral pain during active labour. 914 Oct 79

Omapatrilat represents a new class of drugs capable of inhibiting both ACE and neutral endopeptidase 24.11, the so-called vasopeptidase inhibitors. It therefore contributes to neurohumoral modulation, which might improve endothelial function in cardiovascular diseases. This study investigated the effect of omapatrilat in comparison to the ACE inhibitor captopril on systolic blood pressure and endothelial function in salt-induced hypertension. Dahl salt-sensitive rats (n=6/group) on standard or salt-enriched (4% NaCl) chow were treated for 8 weeks with either omapatrilat (36+/-4 mg/kg per day), captopril (94+/-2 mg/kg per day), or placebo. Aortic rings were then isolated and suspended in organ chambers for isometric tension recording. Systolic blood pressure of salt-fed, placebo-treated animals increased to 196+/-6 mm Hg, which was prevented by omapatrilat (162+/-5 mm Hg, P<0.05) and captopril (164+/-7 mm Hg, P<0.05) to a comparable degree. In control rats, acetylcholine (10(-10) to 10(-5) mol/L) induced endothelium-dependent relaxation (97+/-4%), which was reduced by high-salt diet to 30+/-5% (P<0.005; n=6). Omapatrilat improved relaxation to a greater extent (86+/-5%) than did captopril (57+/-6%; P<0.05). eNOS protein expression and aortic nitrite/nitrate content were reduced in hypertensive rats and improved by both omapatrilat and captopril. Aortic endothelin-1 levels were increased in salt-fed animals and unaffected by omapatrilat or captopril. These data suggest that despite comparable blood pressure, omapatrilat is superior to captopril in improving endothelium-dependent relaxation in salt-sensitive hypertension.
 ...
PMID:Vasopeptidase inhibition exhibits endothelial protection in salt-induced hypertension. 1130 11

The present study was aimed at investigating whether the regulation of vascular renin-angiotensin and endothelin (ET) systems is altered by a chronic blockade of nitric oxide (NO) synthesis. Male Sprague-Dawley rats were supplemented with N(G)-nitro-L-arginine methyl ester (L-NAME, 100mgl(-1)) in drinking water for 4 weeks to inhibit the endogenous synthesis of NO. The mRNA expressions of renin, angiotensin converting enzyme (ACE), type-1 angiotensin II receptor (AT1R), ET-1, type-A ET receptor (ET(A)), and neutral endopeptidase (NEP) were determined in the thoracic aorta by reverse transcription-polymerase chain reaction. The treatment with L-NAME significantly increased the blood pressure, while it decreased the tissue levels of nitrite/nitrate. The mRNA expression of renin, ACE, and AT1R was increased in the aorta. The protein expression of AT1R assessed by Western blot analysis was also increased. The expression of ET-1 and ET(A) mRNA was increased, whereas that of NEP mRNA decreased. The increased expression of renin-angiotensin and ET system genes and the decreased expression of NEP may in part be causally related with the development of hypertension induced by a chronic blockade of NO synthesis.
 ...
PMID:Upregulation of vascular renin-angiotensin and endothelin systems in rats inhibited of nitric oxide synthesis. 1241 41

Nitrogen is one of the crucial elements that regulate plant growth and development. It is well-established that plants can acquire nitrogen from soil in the form of low-molecular-mass compounds, namely nitrate and ammonium, but also as amino acids. Nevertheless, nitrogen in the soil occurs mainly as proteins or proteins complexed with other organic compounds. Proteins are believed not to be available to plants. However, there is increasing evidence to suggest that plants can actively participate in proteolysis by exudation of proteases by roots and can obtain nitrogen from digested proteins. To gain insight into the process of organic nitrogen acquisition from proteins by leek roots (Allium porrum L. cv. Bartek), casein, bovine serum albumin and oxidized B-chain of insulin were used; their degradation products, after exposure to plant culture medium, were studied using liquid chromatography-mass spectrometry (LC-MS). Casein was degraded to a great extent, but the level of degradation of bovine serum albumin and the B-chain of insulin was lower. Proteases exuded by roots cleaved proteins, releasing low-molecular-mass peptides that can be taken up by roots. Various peptide fragments produced by digestion of the oxidized B-chain of insulin suggested that endopeptidase, but also exopeptidase activity was present. After identification, proteases were similar to cysteine protease from Arabidopsis thaliana. In conclusion, proteases exuded by roots may have great potential in the plant nitrogen nutrition.
 ...
PMID:Degradation of proteins by enzymes exuded by Allium porrum roots - a potentially important strategy for acquiring organic nitrogen by plants. 1954 Jul 70

Nitric oxide (NO) and atrial natriuretic peptide (ANP) may induce vascular relaxation by increasing the production of cyclic guanosine monophosphate (cGMP), an important mediator of vascular tone during sepsis. This study aimed to determine whether regulation of NO and the ANP system is altered in lipopolysaccharide (LPS)-induced kidney injury. LPS (10 mg.kg(-1)) was injected in the tail veins of male Sprague-Dawley rats; 12 hours later, the kidneys were removed. Protein expression of NO synthase (NOS) and neutral endopeptidase (NEP) was determined by semiquantitative immunoblotting. As an index of synthesis of NO, its stable metabolites (nitrite/nitrate, NOx) were measured using colorimetric assays. mRNA expression of the ANP system was determined by real-time polymerase chain reaction. To determine the activity of guanylyl cyclase (GC), the amount of cGMP generated in response to sodium nitroprusside (SNP) and ANP was calculated. Creatinine clearance decreased and fractional excretion of sodium increased in LPS-treated rats compared with the controls. Inducible NOS protein expression increased in LPS-treated rats, while that of endothelial NOS, neuronal NOS, and NEP remained unchanged. Additionally, urinary and plasma NOx levels increased in LPS-treated rats. SNP-stimulated GC activity remained unchanged in the glomerulus and papilla in the LPS-treated rats. mRNA expression of natriuretic peptide receptor (NPR)-C decreased in LPS-treated rats, while that of ANP and NPR-A did not change. ANP-stimulated GC activity reduced in the glomerulus and papilla. In conclusion, enhancement of the NO/cGMP pathway and decrease in ANP clearance were found play a role in the pathogenesis of LPS-induced kidney injury.
 ...
PMID:Altered Regulation of Renal Nitric Oxide and Atrial Natriuretic Peptide Systems in Lipopolysaccharide-induced Kidney Injury. 2212 59

Autophagy is present at a basal level in all plant tissues and is induced during leaf ageing and in response to nitrogen (N) starvation. Nitrogen remobilization from the rosette to the seeds is impaired in autophagy mutants. This report focuses on the role of autophagy in leaf N management and proteolysis during plant ageing. Metabolites, enzyme activities and protein contents were monitored in several autophagy-defective (atg) Arabidopsis mutants grown under low and high nitrate conditions. Results showed that carbon (C) and N statuses were affected in atg mutants before any senescence symptoms appeared. atg mutants accumulated larger amounts of ammonium, amino acids and proteins than wild type, and were depleted in sugars. Over-accumulation of proteins in atg mutants was selective and occurred despite higher endopeptidase and carboxypeptidase activities. Specific over-accumulation of the ribosomal proteins S6 and L13 subunits, and of catalase and glutamate dehydrogenase proteins was observed. atg mutants also accumulated peptides putatively identified as degradation products of the Rubisco large subunit and glutamine synthetase 2 (GS2). Incomplete chloroplast protein degradation resulting from autophagy defects could explain the higher N concentrations measured in atg rosettes and defects in N remobilization. It is concluded that autophagy controls C : N status and protein content in leaves of Arabidopsis.
 ...
PMID:Physiological and metabolic consequences of autophagy deficiency for the management of nitrogen and protein resources in Arabidopsis leaves depending on nitrate availability. 2364 84

Heart failure causes significant morbidity and mortality, with recognised underutilisation rates of guideline-based therapies. Our aim was to review current evidence for heart failure treatments and derive a mnemonic summarising best practice, which might assist physicians in patient care. Treatments were identified for review from multinational society guidelines and recent randomised trials, with a primary aim of examining their effects in systolic heart failure patients on mortality, hospitalisation rates and symptoms. Secondary aims were to consider other clinical benefits. MEDLINE and EMBASE were searched using a structured keyword strategy and the retrieved articles were evaluated methodically to produce an optimised reference list for each treatment. We devised the mnemonic BANDAID (2) , standing for beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine (or potentially neprilysin inhibitor), diuretics, aldosterone antagonist, ivabradine, devices (automatic implantable cardioverter defibrillator, cardiac resynchronisation therapy or both) and digoxin as a representation of treatments with strong evidence for their use in systolic heart failure. Treatment with omega-3 fatty acids, statins or anti-thrombotic therapies has limited benefits in a general heart failure population. Adoption of this mnemonic for current evidence-based treatments for heart failure may help improve prescribing rates and patient outcomes in this debilitating, high mortality condition.
...
PMID:Beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, nitrate-hydralazine, diuretics, aldosterone antagonist, ivabradine, devices and digoxin (BANDAID(2) ): an evidence-based mnemonic for the treatment of systolic heart failure. 2610 36


1 2 Next >>