Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The protease inhibitors Trasylol and soyabean trypsin inhibitor prevented the activation of plasma inactive renin by acid. 2. N-Ethylmaleimide inhibited acid-activation to some extent but o-phenathroline had no effect. 3. Acid-activation of the inactive renin in human plasma is mediated by a serine protease.
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PMID:An endogenous protease activating plasma inactive renin. 3 3

The trypsin inhibitor of bovine colostrum was isolated by affinity chromatography, and impurities removed by trichloroacetic acid precipitation. The inhibitor showed electrophoretic microheterogeneity which was not due to sialic acid content. It inhibited bovine and rat trypsin, showed weak inhibition of bovine chymotrypsin and was inactive against rat chymotrypsin and bovine renin, kallikrein, thrombin and trypsinogen. The dynamics of secretion of the inhibitor in the first 8 milkings post-partum were very similar to those of colostral immunoglobulins.
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PMID:Isolation and properties of bovine colostral trypsin inhibitor. 10 61

1. The mechanism of increased renin activity after human plasma had been kept at -5 degrees C for 4 days (cryoactivation) was investigated. 2. The increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0.88, P less than 0.001, n = 10). 3. An inhibitor of thiol enzyme, N-ethylmaleimide did not inhibit cryoactivation. 4. Soyabean trypsin inhibitor and di-isopropylflurophosphate (DFP) inhibited cryoactivation, suggesting that the cryoactivation may be due to the action of a trypsin-like serine enzyme. 5. In an experiment in the rat haemorrhagic shock caused parallel and cryoactivated plasma, the renin activity being about two times higher in the latter. No significant differences were found in the concentrations of renin and renin substrate between the non-cryoactivated and cryoactivated plasma samples. 6. The results may indicate that a destruction of an inhibitor of the renin-renin substrate reaction is responsible for the increase of renin activity after exposure of rat plasma to low temperature. A trypsin-like enzyme in plasma might have destroyed the inhibitor during this procedure.
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PMID:Cryoactivation of plasma renin. 28 40

The mechanism of the increase in renin activity in human plasma which had been kept -5 degrees C for 4 days (cryoactivation) was investigated. From the results of clinical studies, it is likely that the controling mechanism of inactive renin has something in common with that of active renin. The experimental data showed that the increase in renin activity of human plasma by cryoactivation was closely correlated to the increase obtained by incubation with trypsin (r = 0.88, p less than 0.001, n = 10). Soybean trypsin inhibitor, aprotinin and di-isopropylfluorophosphate (DFP) inhibited cryoactivation, indicating that the cryoactivation is due to the action of a trypsin-like serine enzyme. Trypsin which had no effect on plasma renin activity in the presence of the same amount of soybean trypsin inhibitor at 37 degrees C, activated the renin activity during cold incubation, suggesting that the dissociation of the trypsin-inhibitor complex may have taken place at a low temperature. Endogenous trypsin inhibitor is also likely to lose its affinity to endogenous trypsin-like enzyme at a low temperature.
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PMID:Cryoactivation of inactive renin in human plasma. 31 80

Human renin is synthesized as a 406-amino acid preprorenin protein that is processed by a signal peptidase during secretion, to release prorenin as a 386-amino acid zymogen. The 46-amino acid "pro" domain is removed by a renin-processing enzyme, to produce enzymatically active renin, by cleavage at an Arg-Leu bond. The effects of the renin-processing enzyme can be mimicked by trypsin activation, where high concentrations of trypsin are incubated with prorenin for brief periods of time, followed by excess trypsin inhibitor to minimize secondary proteolytic processing by trypsin. In order to study the role of the pro segment in the secretion, folding, and activity of human renin, we engineered a construct where the pro domain from the preprorenin cDNA was deleted. This construct was introduced into mammalian cells and its expression was assayed in transient and stable systems. In COS-1 cells transfected with the prerenin expression vector pREN3, active renin was secreted with a specific activity of 1360 micrograms of angiotensin l/min/mg, compared with trypsin-activated prorenin, which has a specific activity of 818 micrograms of angiotensin l/min/mg. The active renin secreted in this system had a significantly reduced potency for the renin inhibitor SQ 32,970. These results demonstrate that the pro segment is dispensable for the folding and secretion of renin. A permanent cell line expressing the active form of renin was obtained by co-transfection of NRP cells with pREN3 and pHyg. A colony designated B/1 was identified, subcloned, and shown to secrete active renin (110 pg of renin/10(6) cells) optimally when maintained in both G418 and hygromycin.
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PMID:Stable expression, secretion, and characterization of active human renin in mammalian cells. 173 22

Enzymatic activity of tonin-alpha 1-macroglobulin complex was studied in vitro and in vivo, using an immunoimmobilization technique. Tonin-alpha 1-macroglobulin complex, which was immunologically immobilized by anti-alpha 1-macroglobulin antibody covalently coupled to agarose gels, could quantitatively hydrolyze angiotensin I and synthetic tridecapeptide renin substrate to form angiotensin II. However, the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex could not hydrolyze the plasma protein renin substrate. Phenylmethylsulfonyl fluoride, a serine protease inhibitor, inhibited both free tonin and the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex. The hydrolytic activity of the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex against angiotensin I was not inhibited by soybean trypsin inhibitor (molecular weight, 23,000), a potent inhibitor of free tonin. Taken together, these results suggest that tonin bound to alpha 1-macroglobulin keeps the active site intact and that inhibition of the enzyme activity is due to a steric hindrance. When 500 microliter of tonin was administered intravenously to rats, the immunoimmobilization method was used to show that the tonin-alpha 1-macroglobulin complex in the plasma formed angiotensin II. Thus, the tonin-alpha 1-macroglobulin complex in the plasma may be linked to some forms of hypertension through angiotensin II formation.
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PMID:Formation of angiotensin II by tonin-inhibitor complex. 244 41

A highly active angiotensin-producing enzyme (enzyme III) was obtained from the serum of bilaterally nephrectomized dogs by acid treatment and ammonium sulfate fractionation. An inactive precursor (proenzyme III) was converted to enzyme III during prolonged storage (or by treatment with acid or with cathepsin G or by incubation at 38 degrees C as described in the following paper). Enzyme III reacted maximally at pH 7.7 and it produced up to 400 ng of angiotensin II/mL serum/h (i.e., amounts 4000 times higher than that generated by the endogenous renin present in serum after bilateral nephrectomy). Enzyme III produced angiotensin II at identical rates when either dog angiotensinogen or angiotensin I was used as substrate, but the rate was 710 times higher with synthetic tetradecapeptide renin substrate. Enzyme III is not identical to renin, cathepsin G, tonin, enzyme I, enzyme II, the calcium-dependent angiotensin I-converting enzyme, or the calcium-independent carboxy peptidase, which acts by sequential cleavage of angiotensin I. Enzyme III was inhibited by alpha-1-antitrypsin, diisopropyl fluorophosphate, and lima bean trypsin inhibitor (hence it is a serine proteinase). It was not inhibited by Captopril, Teprotide, or Enalapril. It had been reported previously that cathepsin G released from neutrophil granulocytes, by producing high local concentrations of angiotensin II, may provide a mobile means for modulating blood flow in tissue microvasculature during the inflammatory response. The present study offers a new, additional pathway, by enzyme III, for a similar rapid formation of angiotensin II from serum protein substrate or angiotensin I.
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PMID:Angiotensin II-producing enzyme III from acidified serum of nephrectomized dogs. 257 42

Enzyme III and its inactive precursor proenzyme III have been obtained from the acidified serum of bilaterally nephrectomized dogs. Enzyme III occurs in a concentration producing angiotensin at a rate 50 times higher than the residual renin. Much higher concentrations of enzyme III have been obtained by three activation procedures: a) by storage for several months in the frozen state; b) by treatment at 0 degrees C and pH 3.0; or c) by incubation at 38 degrees C and pH 7.7. These procedures yielded levels of enzyme III that produced up to 400 ng angiotensin II/mL serum/h, i.e., 4000 times higher than the endogenous renin. Of further significance, the angiotensin II produced by enzyme III represents the octapeptide with the highest known vasoconstrictor activity. This is in contrast to renin, enzyme I, and enzyme II, all of which produced angiotensin I, the decapeptide without appreciable vasoconstrictor activity. The endogenous activating enzyme has been identified as cathepsin G by the following six experimental observations: both the endogenous activating enzyme and exogenous cathepsin G produced enzyme III from proenzyme III according to the same unusual sigmoid kinetics; they were blocked identically by antibody to human cathepsin G. Also, both were inhibited similarly by alpha-1-antitrypsin, lima bean trypsin inhibitor, diisopropyl fluorophosphate, or by an inhibitor present in dog serum. Thus, removal of this inhibitor and activation of proenzyme III by endogenous or by added cathepsin G are prerequisites to obtaining enzyme III; this provides a novel mechanism for the rapid formation of angiotensin II from serum protein substrate or from angiotensin I.
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PMID:Angiotensin II-producing enzyme III from acidified serum of nephrectomized dogs. Activation of proenzyme III to enzyme III by cathepsin G. 280 76

A method for trypsin-activation of dog plasma inactive renin is described. Liquid phase trypsin (final concentration 6.7 mg/ml) was used and the reaction was stopped after 2 min at 4 degrees C by soybean trypsin inhibitor (13 mg/ml). Renin was measured as angiotensin I (Ang I) generation in trypsin-treated and untreated plasma using the antibody-trapping method, in the presence of excess ox renin substrate. The renin-like activity after trypsin was indeed due to renin, since Ang I generation in dog plasma before and after trypsin treatment was completely inhibited by H-77 at 10(-6) mol/l, and the two IC50 values were very similar (2.7 +/- 0.7 and 2.9 +/- 0.7 at 10(-8) mol/l, respectively). Dog plasma inactive renin was effectively separated from active renin by chromatography on Affigel Blue. Like human prorenin, dog plasma inactive renin rose in response to sodium depletion (furosemide 5 mg/kg, i.v.) followed by a low-salt diet (1 mmol Na+/day) for 4 days, (from 29.6 +/- 8 to 162 +/- 22 microU/ml; P less than 0.01, n = 10). Active renin also increased as expected. Intravenous captopril (6 mg/kg per h), for 3 h, led to a sharp increase in dog plasma active renin (from 53 +/- 8 to 360 +/- 60 microU/ml; P less than 0.01, n = 6), whereas inactive renin remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Similarity between active and trypsin-activated inactive renin in dog plasma by means of renin inhibition: the dog as an animal model for studies of inactive renin. 306 12

The mechanisms causing the release of plasma inactive renin (PIR) area still unclear. We have investigated the role of the kidney in the release of trypsin-activable PIR from extrarenal sources in the rat, with special reference to the submandibular gland. The activation of PIR was performed by incubation with 20 mg/ml trypsin at 4 degrees C for up to 10 min; the reaction was then terminated by addition of 20 mg/ml of soybean trypsin inhibitor. Bilateral nephrectomy resulted in a gradual, marked, sex-independent increase in PIR concentration, reaching levels 4.5 times higher than basal in 24 h (time 0: 14.8 +/- 1.0 ng/ml per h; 24 h: 66.8 +/- 3.4 ng/ml per h, mean +/- s.d., P less than 0.001). This increase was not altered by the concomitant intravenous infusion of pressor doses of either angiotensin (Ang) II (30 ng/min) or pure mouse submandibular renin (a 20-ng intravenous bolus followed by intravenous infusion at the rate of 50 ng/h) for 4 h, but was completely prevented by prior removal of the submandibular glands, in which no activity of active renin and no inactive renin was detected. These results suggest that the post-nephrectomy increase of PIR is not dependent on feedback mechanisms of the suppressed renin-angiotensin system, but is controlled by the presence of submandibular glands in the rat.
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PMID:Reno-submandibular axis controls release of extrarenal inactive renin. 328 Jun 71


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