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

Tree carbon (C) uptake (net primary productivity excluding fine root turnover, NPP') in a New Zealand Pinus radiata D. Don plantation (42 degrees 52' S, 172 degrees 45' E) growing in a region subject to summer soil water deficit was investigated jointly with canopy assimilation (A(c)) and ecosystem-atmosphere C exchange rate (net ecosystem productivity, NEP). Net primary productivity was derived from biweekly stem diameter growth measurements using allometric relations, established after selective tree harvesting, and a litterfall model. Estimates of A(c) and NEP were used to drive a biochemically based and environmentally constrained model validated by seasonal eddy covariance measurements. Over three years with variable rainfall, NPP' varied between 8.8 and 10.6 Mg C ha(-1) year(-1), whereas A(c) and NEP were 16.9 to 18.4 Mg C ha(-1) year(-1) and 5.0-7.2 Mg C ha(-1) year(-1), respectively. At the end of the growing season, C was mostly allocated to wood, with nearly half (47%) to stems and 27% to coarse roots. On an annual basis, the ratio of NEP to stand stem volume growth rate was 0.24 +/- 0.02 Mg C m(-3). The conservative nature of this ratio suggests that annual NEP can be estimated from forest yield tables. On a biweekly basis, NPP' repeatedly lagged A(c), suggesting the occurrence of intermediate C storage. Seasonal NPP'/A(c) thus varied between nearly zero and one. On an annual basis, however, NPP'/A(c) was 0.54 +/- 0.03, indicating a conservative allocation of C to autotrophic respiration. In the water-limited environment, variation in C sequestration rate was largely accounted for by a parameter integrative for changes in soil water content. The combination of mensurational data with canopy and ecosystem C fluxes yielded an estimate of heterotrophic respiration (NPP' - NEP) approximately 30% of NPP' and approximately 50% of NEP. The estimation of fine-root turnover rate is discussed.
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PMID:Net ecosystem productivity, net primary productivity and ecosystem carbon sequestration in a Pinus radiata plantation subject to soil water deficit. 1265 99

These studies examined the interactions of neutral endopeptidase (NEP), endothelin-1 (ET-1), and nitric oxide (NO) in deoxycorticosterone acetate (DOCA)-induced hypertension. Male Sprague-Dawley rats (n = 35) were uninephrectomized (UNx) or uninephrectomized and treated with DOCA (25 mg pellet implanted subcutaneously). Candoxatril (30 mg/kg day(-1)), a NEP inhibitor, was given orally for 3 weeks in UNx or DOCA rats. Sham nephrectomized rats (SHAM) served as controls. Except SHAM, all other groups received 1% NaCl in drinking water ad libitum. Measurements were taken of systolic blood pressure (SBP), left ventricle (LV), and aortic weight (AW), plasma ET-1, and urinary excretion of nitrite and Na+. Whole body vascular hypertrophy and morphometric analysis of histological sections of the heart were also determined. In DOCA rats, SBP increased from 113 +/- 5 to 170 +/- 5 mmHg without significant changes in body weight (BW). Candoxatril reduced the increase in SBP to 135 +/- 9 mmHg (P < 0.05), abolished the increased LV wall thickness (P < 0.05), and increased the reduced LV lumen diameter (P < 0.05) in DOCA-salt rats. Candoxatril also reduced plasma ET-1 by 88 +/- 9% and 89 +/- 17% (P < 0.05) in UNx and DOCA rats, respectively, and elicited increases in urinary excretion of nitrite. These effects were accompanied by a marked increase in urinary excretion of Na+ (U(Na)V) (P < 0.05) and a blunting of the proteinuria (32 +/- 5%; P < 0.05) in DOCA rats. We conclude that endopeptidase inhibition in DOCA-salt hypertension reduced the increase in blood pressure and the attendant tissue hypertrophy and renal injury. These effects suggest a correlation between endopeptidase-related reduction in ET-1 production and protection in DOCA-salt hypertension.
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PMID:Chronic endopeptidase inhibition in DOCA-salt hypertension: mechanism of cardiovascular protection. 1294 Apr 71

Inhibition of nitric oxide synthases causes systemic hypertension and renal injury in rats. Our objective was to examine whether omapatrilat, a vasopeptidase inhibitor that inhibits both angiotensin-converting enzyme (ACE) and neutral endopeptidase, could induce better regression of renal injury than ACE inhibitor alone. Ten groups of rats were studied. They were fed either a normal (0.8% NaCl) or a high (4% NaCl) sodium diet. Eight of these groups received NG-nitro-L-arginine methyl ester (L-NAME, 20 mg x kg(-1) x d(-1)) in their drinking water. After 4 weeks, 1 group on each diet was killed and considered the L-NAME group, whereas the others received L-NAME alone, captopril (200 mg x kg(-1) x d(-1)) plus L-NAME, or omapatrilat (80 mg x kg(-1) x d(-1)) plus L-NAME for 4 additional weeks. In rats receiving L-NAME alone for 8 weeks, the mortality rate was approximately 90%, irrespective of the diet. In contrast, all rats survived in the captopril and the omapatrilat groups. In rats fed a normal-sodium diet, captopril and omapatrilat normalized systolic blood pressure and induced a complete regression of renal injury. Creatinine clearance and proteinuria were also normalized. In the high-sodium-diet groups, both treatments were less efficient: blood pressure remained elevated, and the regression of renal fibrosis was only partial. Although proteinuria decreased significantly with captopril or omapatrilat, creatinine clearance remained lower than in the controls. These results demonstrate that, in nitric oxide-deficient rats fed a normal-sodium diet, ACE and vasopeptidase inhibitors exhibit a marked renoprotective effect, whereas these treatments are less efficient in rats fed a high-sodium diet.
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PMID:Renal effects of omapatrilat and captopril in salt-loaded, nitric oxide-deficient rats. 1456 1

Reaction of one equivalent of vanadium(III) chloride with three equivalents of l-cysteine(H2Cys) in methyl alcohol affords a VIII-Cys compound that is formulated as [VIII(Hcys)3].2HCl.2.5H2O 1. The solid state characterization of 1 was performed by microanalysis, circular dichroism (CD) and infrared studies as well as room temperature magnetic susceptibility. These studies have shown coordination of each HCys- ligand to the VIII atom through an amine nitrogen and a carboxylate oxygen atoms. Solution studies of 1 were carried out in water and methanol by UV-visible, CD and electron paramagnetic resonance (EPR) spectroscopies. According to these studies, it was evident that despite the progressive oxidation of 1 to oxovanadium(IV) species, some V(III) species were also present in solution after several hours. Compound 1, VIVOSO4.5H2O and l-cysteine were examined for their total antioxidant capacity (TAC) and lag time. Compound 1 exhibited significantly greater total antioxidant capacity and lag time values than l-cysteine. VIVOSO4.5H2O did not show any total antioxidant capacity or lag time. The inhibition of neutral endopeptidase (NEP) activity caused by 1, VIVOSO4.5H2O and thiorphan was also measured. Compound 1, at a concentration of 10(-3) M, showed inhibition of NEP activity as potent as thiorphan at 10(-6) M, while VIVOSO4.5H2O in the same concentration exhibited less than 50% inhibitory activity than that of thiorphan at 10(-6) M. Moreover, the antimetastatic effects of compound 1, l-cysteine and VIVOSO4.5H2O were examined on Wistar rats, treated with 3,4-benzopyrene. The results revealed that 1 prevents significantly lung metastases (only 9.5% of animals treated with 1 showed metastases), whereas 47-52% of the rats of the control group and those treated with l-cysteine and VIVOSO4.5H2O exhibited metastases.
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PMID:Solid state and solution studies of a vanadium(III)-L-cysteine compound and demonstration of its antimetastatic, antioxidant and inhibition of neutral endopeptidase activities. 1514 2

The chronic treatment of rats with N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) biosynthesis, results in hypertension. This inhibition of NO production results in activation of the renin-angiotensin system, with increased activity of the carboxypeptidase angiotensin I-converting enzyme (ACE). Since chronic NO inhibition increases ACE activity, we hypothesized that this inhibition could also affect the activities of other peptidases involved in cardiovascular functions. To test this possibility, we examined the activities of aminopeptidase M (APM), dipeptidyl peptidase IV (DPP IV), metalloendopeptidase 24.15 (MEP 24.15) and neutral endopeptidase 24.11 (NEP 24.11) in rat brain, heart, kidney, liver, lung and thoracic aorta. Male Wistar rats were treated chronically with L-NAME (80mgkg(-1) per day) administered in the drinking water for 4 weeks and their organs then removed and processed for the determination of peptidase activities. Treatment with L-NAME did not significantly alter the activities of the four peptidases in brain, heart, kidney, liver and lung. In contrast, in aorta, the activity of APM was slightly but significantly reduced whereas those of DPP IV and MEP 24.15 were markedly enhanced; NEP 24.11 was not detected in this tissue. Immunoblotting for DPP IV and MEP 24.15 showed increased expression in aortic tissue. Neither L-NAME (1-100microM) nor the NO donors sodium nitroprusside and 3-morpholinosydnonimine (SIN-1; 1-100microM) had any consistent effect on the activity of recombinant MEP 24.15 or renal DPP IV. The importance of MEP 24.15 in peptide metabolism was confirmed in pentobartibal-anesthetized rats pretreated with the MEP 24.15 inhibitor N-[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Aib-Tyr-p-aminobenzoate (JA2), which significantly potentiated the hypotensive response to bradykinin. The altered peptidase activities seen in aorta may contribute to modulating vascular responses in this model of hypertension.
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PMID:Peptidase activities in rats treated chronically with N(omega)-nitro-L-arginine methyl ester (L-NAME). 1519 92

In this study, we compared the properties of a serine endopeptidase H1 (SH1) and a serine thiol endopeptidase (STH2) purified from human urine by DEAE-cellulose followed by a Bio Gel A0.5 m or Sepharose Mercurial chromatographs. These enzymes differ in their action upon different hormone peptides. We used fluorogenic substrates to further characterize the enzyme. The substrate specificity of urinary SH1 was studied using different internally quenched fluorescent peptides, and AbzFGQEDDnp was hydrolyzed by SH1. Other enzymes present in urine, such as serine endopeptidase H2, prolyl endopeptidase, neutral endopeptidase like and angiotensin-I converting enzyme, were not able to hydrolyze this substrate. SH1 is 100% inhibited by PMSF and resistant to EDTA, OPA, thiorphan, E64, pOHMB and phosphoramidon. Endopeptidase STH2 is completely inhibited by PMSF, E64 and pOHMB. Enzyme SH1 hydrolyzes the peptide bound F5-S6 at bradykinin (BK: RPPGFSPFR) molecule and R-Q at AbzBKQEDDnp. When studying enzyme STH2, the cleavage sites determined to the related substrates were F5-S6 using BK as substrate and F-R using AbzBKQEDDnp. The kilometers value obtained for AbzBKQEDDnp and AbzFGQEDDnp were 1.18 and 0.007 uM, respectively. Kininases from kidney and urine can hydrolyze peptide bounds from components of the kallikrein-kinin system, the angiotensin-renin system and the neuropeptides system, straight contributing in kidney homeostasis. SH1 was located at the distal tubule [Casarini et al., 1999a, Am. J. Physiol. 277, F66] and can have an important function in the control of kinin found in this portion, since is known that all components of the kallikrein-kinin system were found in this portion. The physiological role of SHT2 could be related to the inter-relation between the kallikrein-kinin system and neuropeptides in the control of the water electrolyte balance [Braz. J. Med. Biol. Res. 25 (3) (1992) 219].
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PMID:Specificity comparison of a serine endopeptidase (SH1) and a serine thiol endopeptidase (STH2) purified from human urine. 1520 8

In this paper, we review our current understanding of the medicinal chemistry of the major peptide systems, which influence body fluid homeostasis. Electrolytes play pivotal roles in intra- and intercellular communication, acid-base equilibrium and, when bound to several macromolecules, they regulate a myriad of enzymatic proteins, receptors and transcription factors. Cell turgor influences the plasma membrane, which activates mechanically-gated ion channels or mechanoreceptors, and the expression of a number of genes which underlie long-term metabolic responses to hormones, substrates and reactive oxygen intermediates. The altered kinetics and enzymatic cleavage of peptides during water-electrolyte imbalance can contribute to cardiac and renal damage associated with elevated blood pressure. Identification of the enzymes which are responsible for cleavage, together with emerging information about the mechanisms of action and structures of regulatory and effector peptides, has laid a foundation for the discovery of novel drugs, some of which are in use or are now undergoing evaluation in experimental trials. The development of models of hydrosaline challenge with relative efficiency to induce selective water-electrolyte imbalance has permitted the identification of kallikrein-kinin, renin-angiotensin-aldosterone, vasopressin-oxytocin, thyrotropin-releasing hormone and luteinizing hormone-releasing hormone as susceptible substrates. At present, the angiotensin-I converting enzyme inhibitors are well-known efficacious, orally active, blood pressure-lowering agents which have been used in hypertensive patients. In addition to several new analogues of this class of drug, some selective dual inhibitors of angiotensin-I converting enzyme and neutral endopeptidase and inhibitors of aminopeptidases are now also being rationally assayed and their beneficial effects on hypertension and hydromineral balance indicate that this type of drug may have powerful therapeutic effects for disorders of body fluid homeostasis.
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PMID:Peptide metabolism and the control of body fluid homeostasis. 1532 Jul 88

Omapatrilat (OMP) is a novel mixed inhibitor of angiotensin-converting enzyme (ACE) and neutral endopeptidase 24.11 (NEP), the enzyme that metabolizes natriuretic peptides. Congestive heart failure (CHF) is characterized by excessive sodium retention, attributed to both an excessive effect of angiotensin II and diminished responsiveness to natriuretic peptides. In this study, we examined the acute and chronic renal and cardiac effects of OMP in rats with compensated [urinary sodium excretion (UNaV) > 1,200 microeq/day] and decompensated (UNaV < 100 microeq/day) CHF, induced by a surgical aortocaval fistula (ACF). Bolus injection of OMP (10 mg/kg) to sham controls produced significant diuretic and natriuretic responses [UNaV increased from 0.67 +/- 0.19 to 3.27 +/- 1.35 microeq/min, P < 0.05; fractional sodium excretion (FENa) increased from 0.23 +/- 0.06 to 0.95 +/- 0.34%, P < 0.01] despite a significant decline in blood pressure (BP). Rats with compensated CHF displayed blunted diuresis and natriuresis to this dose of OMP but a significant decrease in BP. However, in rats with decompensated CHF, OMP induced significant natriuresis (FENa increased from 0.18 +/- 0.15 to 0.82 +/- 0.26%, P < 0.05) despite a further decrease in BP (from 90 +/- 9 to 71 +/- 6 mmHg, P < 0.01). Two weeks after ACF, the heart/body weight ratio was significantly greater in rats with CHF than controls (0.51 +/- 0.026 vs. 0.30 +/- 0.004%, P < 0.0001), and UNaV was significantly lower. Immediate or late (1 or 6 days after ACF) OMP treatment in the drinking water (140 mg/l) reduced cardiac hypertrophy to 0.41-0.43% (P < 0.01) and induced natriuresis. These results suggest that OMP improves both sodium balance and cardiac remodeling and might be advantageous to ACE inhibitors for the treatment of decompensated CHF.
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PMID:Cardiac and renal effects of omapatrilat, a vasopeptidase inhibitor, in rats with experimental congestive heart failure. 1549 26

Conditions for carrying out chemically targeted identification of peptides containing phosphorylated or glycosylated serine residues have been investigated. Ba(OH)2 was used at ambient temperature to catalyze the beta-elimination reaction at 25 degrees C. Nucleophilic addition of 2-aminoethanethiol was performed in both parallel and tandem experiments. The method was demonstrated by the reaction of beta-casein tryptic digest phosphopeptides and an O-glycosylated peptide. Contrary to an earlier report by others, the glycopeptide was found to react with essentially the same kinetics as phosphopeptides. Conversion of four phosphoserines in residues 15, 17, 18, and 19 from bovine beta-casein N-terminal tryptic phosphopeptides were followed by monitoring the time course of the addition reaction. The chemistry proceeded rapidly at room temperature with a half-reaction time of 15 min. No side-reaction products were observed; however, care was taken to minimize all counter ions that either precipitate barium or neutralize the base. Digestion of the converted peptides with lysine endopeptidase identified all five phosphoserines in the beta-casein tryptic digest. Alternatively, preincubation with base followed by nucleophilic addition of the thiol was found to work satisfactorily. The use of the water-soluble hydrochloride of 2-aminoethanethiol allowed beta-elimination, nucleophilic addition, and desalting to be carried out on a micro C18 reverse phase pipette tip.
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PMID:Reaction of phosphorylated and O-glycosylated peptides by chemically targeted identification at ambient temperature. 1558 26

Alzheimer's disease (AD) is a progressive neurodegenerative disorder for which there are few therapeutics that affect the underlying disease mechanism. Recent epidemiological studies, however, suggest that lifestyle changes may slow the onset/progression of AD. Here we have used TgCRND8 mice to examine directly the interaction between exercise and the AD cascade. Five months of voluntary exercise resulted in a decrease in extracellular amyloid-beta (Abeta) plaques in the frontal cortex (38%; p = 0.018), the cortex at the level of the hippocampus (53%; p = 0.0003), and the hippocampus (40%; p = 0.06). This was associated with decreased cortical Abeta1-40 (35%; p = 0.005) and Abeta1-42 (22%; p = 0.04) (ELISA). The mechanism appears to be mediated by a change in the processing of the amyloid precursor protein (APP) after short-term exercise, because 1 month of activity decreased the proteolytic fragments of APP [for alpha-C-terminal fragment (alpha-CTF), 54% and p = 0.04; for beta-CTF, 35% and p = 0.03]. This effect was independent of mRNA/protein changes in neprilysin and insulin-degrading enzyme and, instead, may involve neuronal metabolism changes that are known to affect APP processing and to be regulated by exercise. Long-term exercise also enhanced the rate of learning of TgCRND8 animals in the Morris water maze, with significant (p < 0.02) reductions in escape latencies over the first 3 (of 6) trial days. In support of existing epidemiological studies, this investigation demonstrates that exercise is a simple behavioral intervention sufficient to inhibit the normal progression of AD-like neuropathology in the TgCRND8 mouse model.
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PMID:Voluntary exercise decreases amyloid load in a transgenic model of Alzheimer's disease. 1585 47


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