Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both dietary protein restriction and angiotensin converting enzyme inhibitors (CEI) reduce proteinuria in experimental renal disease. To determine whether the effects of dietary protein on albuminuria (UalbV) in nephrotic rats are modified by CEI, we measured UalbV and glomerular filtration rate (GFR) in rats with passive Heymann nephritis fed 40 (HP) or 8.5% (LP) protein diets. Half of each group received enalapril beginning 2 days after injection of antibody. Enalapril prevented the greater UalbV and fractional clearance of albumin (FCalb) observed in HP (HP + enalapril, 136 +/- 44 mg/day and 0.88 +/- 0.54 X 10(-2), vs. HP, 368 +/- 60 mg/day and 4.40 +/- 2.90 X 10(-2), P less than 0.05 and P less than 0.05, respectively) but did not alter GFR significantly. Enalapril did not alter UalbV or FCalb in LP. To determine if CEI would reduce UalbV in rats after proteinuria was already present, rats fed 21% protein were studied 1 wk after the onset of proteinuria. Enalapril decreased UalbV (423 +/- 35 to 169 +/- 18 mg/day, P less than 0.001) and FCalb (3.19 +/- 0.36 X 10(-2) to 0.71 +/- 0.11 X 10(-2), P less than 0.001) after 3 days. Thus CEI reduced albuminuria in nephrotic rats fed high- or normal-protein diets without modifying GFR or serum albumin. This effect may be due to changes in glomerular hemodynamics or permselectivity.
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PMID:Modulation of albuminuria by dietary protein and converting enzyme inhibition. 282 30

1 Bradykinin in carrageenin-induced inflammatory pouch fluid was measured by an enzyme immunoassay method. 2 The bradykinin showed a single peak in the 30-60 min period after the challenge and then decreased quickly, and there was a correlation between the bradykinin level and exudation of fluorescein-labelled bovine serum albumin in the first 60 min period. 3 Captopril (an inhibitor of kininase II) elevated both the bradykinin level in the inflammatory pouch fluid and vascular permeability, while DL-2-mercaptomethyl-3- guanidinoethylthiopropanoic acid (an inhibitor of kininase I) had no effect. 4 Soybean trypsin inhibitor (SBTI) inhibited the vascular permeability response in parallel with the decrease in the bradykinin level. 5 A bradykinin-degrading activity appeared in the pouch fluid within 1 h after the challenge and increased with time. 6 In the period of 3.5-4 h, bradykinin levels were suppressed below the sensitivity limit of the assay, i.e. 0.07 nm ml-1, in spite of active generation. This was because degradation of bradykinin was very rapid in this late stage. Nevertheless, bradykinin still played a definite role in sustaining a high level of vascular permeability response in the late stage in conjunction with prostaglandins.
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PMID:Role of bradykinin in the vascular permeability response induced by carrageenin in rats. 283 62

Protamine given to neutralize heparin after extracorporeal circulation can trigger a catastrophic reaction in some patients. While searching for a biochemical basis for this reaction, protamine was tested as an inhibitor of human plasma carboxypeptidase N (CPN) or kininase I, the inactivator of anaphylatoxins and kinins. Human plasma and CPN purified from human plasma, (Mr = 280 K) or its isolated active subunit (Mr = 48 K) were the sources of enzyme. The hydrolysis of furylacryloyl (FA)-Ala-Lys was measured in a UV spectrophotometer and that of bradykinin and the synthetic C-terminal octapeptide of anaphylatoxin C3a (C3a8) by high performance liquid chromatography. Protamine inhibited the hydrolysis of FA-Ala-Lys by CPN, (IC50 = 3.2 X 10(-7) M); added human serum albumin (30 mg/ml) increased the IC50 to 7 X 10(-6) M. When plasma was the source of CPN, the IC50 was 2 X 10(-6) M. Protamine more effectively inhibited the hydrolysis of bradykinin and C3a8. The IC50 for protamine was 5 X 10(-8) M with CPN and bradykinin, 7 X 10(-8) M with CPN and C3a8 and with the 48 K subunit and bradykinin it was 7 X 10(-8) M of protamine. Heparin competes with CPN for protamine, because in high concentration (18 U/ml) it reverses the inhibition by protamine. Protamine did not inhibit angiotensin I converting enzyme (kininase II) or the endopeptidase 24.11 (enkephalinase). Kinetic studies showed the mechanism of protamine inhibition to be partially competitive; about 10-20% of the hydrolysis of bradykinin by CPN was not inhibited by protamine. Thus, by blocking the inactivation of mediators released in shock, protamine inhibition of CPN may be partially responsible for the catastrophic reaction observed to occur in some patients.
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PMID:Protamine inhibits plasma carboxypeptidase N, the inactivator of anaphylatoxins and kinins. 291 61

Atrial natriuretic peptide is rapidly degraded by a soluble, heat labile peptidase isolated from ventricular myocytes. Degradation of [125I]-ANP is antagonized by unlabelled ANP, bradykinin, glucagon, 1,10-phenanthroline, PCMB, EDTA and the bacterial antibiotic bacitracin, but not by phenylmethylsulphonyl fluoride, aprotinin, phosphoramidon, E-64, amastatin or the ACE inhibitor SQ 20881 and bradykinin potentiator C. In addition neither bovine serum albumin nor caesin afforded any protection against degradation. Peptidase activity was optimal at pH values above 8.5. The peptidase is likely to be of intracellular origin and may contribute to the extensive ANP degradative activity found in various ventricular muscle preparations.
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PMID:Degradation of [125I]-atrial natriuretic peptide by a soluble metallopeptidase isolated from rat ventricular myocytes. 296 71

A radioimmunoassay was developed for a new, potent inhibitor of angiotensin-converting enzyme (ACE; EC 3.4.15.1), calcium(-)-N-[(S)-3-[(N-cyclohexylcarbonyl-D-alanyl)thio]-2-methyl- propionyl]-L-prolinate (MC-838, altiopril calcium). The antiserum was obtained by immunizing rabbits with MC-838-bovine serum albumin (BSA) conjugate. MC-838-L-tyrosine labeled with 125I and purified by thin-layer chromatography was used as a tracer. The assay sensitivity was 0.1 ng/ml, the average intra-assay coefficient of variation was 7.9%, and the average inter-assay coefficient of variation was 13.7%. The antiserum was specific for MC-838, showing only slight crossreactivity with degradation products of MC-838. After a single oral dose of MC-838 (2 mg/kg), radioimmunoassay of MC-838 canine serum demonstrated rapid absorption from the gastrointestinal tract with a peak level of 40.6 ng/ml. The decline in serum concentration was a biphasic decay, with a half-life of 80 min during rapid falloff followed by a slower decline.
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PMID:A radioimmunoassay for MC-838 (altiopril calcium), a novel angiotensin-converting enzyme inhibitor. 317 83

Microfluorimetric and quantitative cytoenzymatic techniques were employed to examine regional variations in endothelial macromolecular uptake as related to inner mural intermediary metabolism in aortas from normocholesterolemic rabbits. Concomitant reductions in luminal fluorescein isothiocyanate-conjugated bovine serum albumin (FITCBSA) accumulation and succinate (SDH), lactate (LDH) and glucose-6-phosphate (G-6-PDH) dehydrogenase activities were evidenced from ascending to upper abdominal segments. Further diminution of FITCBSA accumulation was observed in the lower abdominal aorta, whereas there was a corresponding elevation of enzyme activities. Highly significant but not exceedingly close correlations were obtained between luminal FITCBSA uptake and inner mural SDH and LDH activities. However, much of the associated variability was attributable to the lower abdominal segment, where there was a microscopically-discernible augmentation in adventitial surface FITCBSA accumulation. The overall data provide direct in vivo support for the concept that endothelial macromolecular transport is coupled to mural oxidative demands, but also indicate that luminal metabolism-permeability relationships are influenced by factors such as extensiveness of the vasoral network and wall thickness. Details of the metabolism-permeability coupling hypothesis and observations implicating metabolic events as basic causative factors underlying vascular pathogenesis are discussed.
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PMID:Metabolism-permeability coupling in the normal rabbit aorta. 370 60

Captopril (SQ 14225) is an inhibitor of angiotensin I-converting enzyme (ACE). Mice with schistosomiasis form granulomas in the liver and intestines that have high ACE activity. We determined whether chronic oral captopril administration would alter the granulomatous response. Infected mice treated with captopril had a dose-dependent decrease in liver granuloma size. Chronic peroral administration of drug induced a sustained decrease in granuloma ACE activity and size which was reversible upon drug withdrawal. The drug was most effective during the acute phase of infection. Granuloma size in the colon, ileum, and ileal Peyer's patches was also decreased by treatment. Ileal granulomas were affected the least. Liver, colon, ileum, and ileal Peyer's patches demonstrated natural differences in size of response to schistosome eggs. Synchronous hypersensitivity granulomas, containing no ACE activity, were generated by the pulmonary embolization of methylated bovine serum albumin-coated, Sepharose beads into sensitized mice. Captopril treatment did not affect the size of these lesions. Sustained improvements in portal pressure, body and liver weight, and water consumption were seen in treated mice. We conclude that captopril induces sustained suppression of the granulomatous response in schistosome-infected mice, which results in decreased morbidity. Circumstantial evidence suggests that captopril influences inflammation through the competitive inhibition of ACE.
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PMID:Alteration of the granulomatous response in murine schistosomiasis by the chronic administration of captopril, an inhibitor of angiotensin-converting enzyme. 626 48

The brain and lung angiotensin converting enzyme (ACE) activities of the rats subjected to haemorrhagic, hypovolemic or endotoxic shock and of the mice immunized and then intravenously challenged with bovine serum albumin were determined by means of a spectrophotometric method. The lung ACE activities of all the shock groups were found significantly higher than those of their Control groups whereas only the brain ACE activities of the rats in endotoxic shock and the mice in anaphylactic shock showed a significant increase compared to their own control values. The results were interpreted as supporting evidence for the idea that peripheral and central renin-angiotensin systems may play a deleterious role in shock.
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PMID:Changes in brain and lung angiotensin converting enzyme activity in various shocks. 633 Jul 68

Quantitative cytochemical and microfluorimetric techniques were employed to compare mural intermediary metabolism--endothelial macromolecular uptake changes in spontaneous aortic-arteriosclerotic lesions of normolipemic New Zealand White rabbits. Specifically, mural succinic (SDH), lactic (LDH), and glucose-6-phosphate (G-6-PDH) dehydrogenase activities and luminal surface uptake of fluorescein isothiocyanate-conjugated bovine serum albumin (FITC-BSA) were measured in lesion sites abnormally resistant (calcified) and susceptible (proliferative) to dietary hypercholesterolemia. Calcified lesions exhibited severe (55-66%) diminution of SDH, LDH, and G-6-PDH activities within the involved inner mural zone and a comparable (68%) decline in luminal FITC-BSA uptake. Concomitant reductions in FITC-BSA uptake (30%) and marker enzymes of the predominant energy transducing pathways in arterial tissue, i.e., SDH (30%) and LDH (31%), were evidenced in proliferative foci, whereas G-6-PDH was augmented (52%) in comparison to nonlesioned aortic segments. These data lend additional support to the concept that endothelial uptake of plasma-borne macromolecules is coupled to oxidizable substrate requirements of inner avascular compartments of the arterial wall. It is postulated that diminished macromolecular transport in these degenerative lesions stems from reduced mural metabolic demands, and that pharmacologic reduction of vascular smooth muscle metabolism may depress uptake of sclerogenic macromolecules.
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PMID:Cytochemical correlates of atherosclerosis-resistant and susceptible lesions of the normal rabbit aorta. 669 4

Cathepsin B was purified about 11,000-fold from monkey skeletal muscle by ammonium sulfate fractionation and sequential column chromatographies monitored by assaying of Z-Phe-Arg-MCA hydrolase activity. The purified enzyme gave a single protein band on SDS-polyacrylamide gel electrophoresis, and its molecular weight was estimated to be 24,000 by gel filtration. It had a pH optimum of 6.5, required a thiol reducing agent for activation, and was inhibited by various thiol protease inhibitors. These properties were similar to those reported for cathepsins B from other sources. Although the enzyme scarcely hydrolyzed ordinary proteins, such as casein, hemoglobin, and bovine serum albumin, it degraded myosin and actin among various myofibrillar proteins. These results strongly suggested that skeletal muscle cathepsin B may participate in the degradation of muscle proteins in vivo. In addition, cathepsin B was shown to hydrolyze various neuropeptides such as Leu-enkephalin, beta-neoendorphin, alpha-neoendorphin, dynorphin(1-13), and substance P. It appeared to act on these peptides mainly as a dipeptidyl carboxypeptidase, although not so rigorously, presumably due to its endopeptidase activity.
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PMID:Purification and characterization of cathepsin B from monkey skeletal muscle. 672 39


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