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:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. An experiment designed to study the relationship between pH and kininogenase activity of three commercial preparations of porcine crystallized pepsin showed that each preparation had two well separated pH optima, pH 4 and 8. 2. From the inhibition spectrum of the pH 8 kininogenase it was concluded that it is a kallikrein of the glandular type, since it proved to be a serine protease and was insensitive to protein trypsin inhibitors. 3. Kallikrein activity can be separated from pepsin by affinity chromatography on Sepharose-4B-Pro-Phe-agmatine. This separation permitted us to obtain purified material with kallikrein specific activity 43 times higher than that of crude pepsin and which showed a single band on polyacrylamide gel electrophoresis. 4. The kallikrein activity was found to have a molecular weight of 36 kDal and a Michaelis constant of 25 microM when acting on Bz-Pro-Phe-Arg-p-nitroanilide at pH 8.6. 5. On the basis of these properties, kallikrein from commercial pepsin resembles the kallikreins previously described from rat or human stomach.
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PMID:Kallikrein isolated from commercial crystalline pepsin preparations. 313 4

A unique tissue kallikrein-binding protein was identified and partially characterized in the brain and serum of Sprague-Dawley rats and in the serum-free conditioned media of mouse anterior pituitary cells (AtT 20) and rodent neuroblastoma x glioma hybrids (NG108-15). Kallikrein and kallikrein-binding protein(s) form SDS- and heat-stable complexes with a molecular weight (Mr) of approximately 92,000. The complex formation of 125I-labelled kallikrein and the binding protein in the serum and brain is inhibited by excess unlabelled rat urinary kallikrein, rat arginine esterase A (a kallikrein-like kininogenase), and human urinary kallikrein. When the active site of kallikrein was blocked by phenylmethylsulfonyl fluoride or D-Phe-D-Phe-L-Arg-CH2Cl, no complex formation was detected. Kallikrein-binding protein only forms complexes with active kallikrein or trypsin-activated prokallikrein but not with prokallikrein. 125I-labelled kallikrein forms a 92-kilodalton protein with binding protein in various brain regions of perfused normotensive rats of the Wistar-Kyoto strain (WKY), including the cerebral cortex, cerebellum and brain stem; but complex formation was not found in corresponding brain regions of the spontaneously hypertensive rat (SHR). Similarly, the kallikrein-binding protein was identified in various tissues including thymus, lung, liver, prostate, Cowper's gland, adrenal gland, kidney, and pancreas of WKY rats but not in tissues of SHR. The results suggest a major difference in the kallikrein-binding protein in hypertensive versus normotensive rats. The role of this specific kallikrein-binding protein in cellular hemodynamic processes and blood pressure regulation remains to be investigated.
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PMID:A major difference of kallikrein-binding protein in spontaneously hypertensive versus normotensive rats. 317 Nov 70

Our studies demonstrate that rat anterior pituitary cells (GH3) are capable of synthesizing and secreting tissue kallikrein together with prolactin and growth hormone. The secretion of prolactin and growth hormone in GH3 cells was measured by two newly developed sensitive radioimmunoassays (RIA), using the polyethylene glycol separation technique. In the direct radioimmunoassay for rat tissue kallikrein, using a polyclonal antiserum which recognizes both active and prokallikrein, the GH3 kallikrein displays parallelism with standard curves of rat urinary kallikrein. The production of immunoreactive kallikrein, prolactin, and growth hormone is time-dependent, and the levels after a 72 h incubation in serum-free media are approximately 12.2 +/- 4.4 ng, 272.2 +/- 33.0 ng, and 475.6 +/- 4.8 ng per 10(6) cells per ml (mean +/- SD, n = 3), respectively. In Western blot analyses, a specific monoclonal antibody to tissue kallikrein (V4D11) identifies GH3-secreted kallikrein as a approximately 39,000 Da protein, slightly larger than approximately 38,000 Da kallikreins of submandibular gland, mouse anterior pituitary cells (AtT 20) or rodent neuroblastoma X glioma hybrid cells (NG108). Kallikrein mRNA in GH3 cells was identified in Northern blot analyses, using a tissue kallikrein cDNA probe. In a RIA using a kallikrein monoclonal antibody (V1C3) recognizing only active kallikrein, kallikrein could not be detected in the media incubated up to 48 h with GH3 cells. However, after trypsin treatment, a time-dependent increase of immunoreactive kallikrein (using monoclonal antibody V1C3), Tos-Arg-OMe esterase, and kinin-releasing activities can be measured in the conditioned media. The activated esterase activity was inhibited by aprotinin and by affinity-purified kallikrein monoclonal antibody (V4D11) in a dose-dependent manner. The data indicated that rat anterior pituitary GH3 cells secrete latent tissue kallikrein, which can be converted to active kallikrein by trypsin. These hormonally responsive cells co-synthesize kallikrein with prolactin and growth hormone and provide a model system for studying the regulation of kallikrein gene expression.
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PMID:Identification of latent tissue kallikrein, prolactin and growth hormone secretion in GH3 pituitary cells using modified radioimmunoassays. 336 Feb 6

We studied the interaction between kallikrein, kinins, and renin release in isolated rat renal glomeruli and their attendant arterioles. Purified hog kallikrein (170 mEU/ml) significantly stimulated renin release 86% (p less than 0.025) above control. Inactivation of kallikrein by PMSF or inhibition with aprotinin blocked kallikrein stimulation of renin release. Partially purified rat submandibular gland kallikrein (160 mEU/ml) also increased renin by 87% (p less than 0.025). Superfusion of glomeruli with bradykinin (10(-5) M) significantly increased renin release by 108% (p less than 0.025), and lys-bradykinin (10(-5) M) similarly increased renin by 155% (p less than 0.025). Neither of the kinin analogues, des-arg9 bradykinin or tyr8 bradykinin (at 10(-5) M), were able to alter renin released from isolated glomeruli. The vasodilator acetylcholine (10(-5) M) had no effect upon renin release from glomeruli. No kininogen could be detected in glomeruli. Kallikrein superfusion did not result in any measurable kinin generation. We could not detect inactive renin in superfusate or glomeruli after renin activation with either kallikrein or trypsin. These results suggest that kallikrein stimulates renin release independent of kininogenase activity and that this stimulation does not appear to be due to activation of inactive renin. Further, we find that kinins can directly stimulate renin release.
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PMID:Kallikrein and kinins independently stimulate renin release from isolated rat glomeruli. 354 14

At equimolar ratio of enzyme/substrate, actin, tropomyosin, fibronectin and myosin were extensively hydrolyzed during an incubation of one hour at 37 degrees C. Dog serum albumin, ovalbumin, bovine gamma-globulin and human prostatic acid phosphatase were not hydrolyzed. The activity of arginine esterase towards actin at pHs 6.5, 7.1 and 7.6 was respectively 60, 74 and 84% of the one found at optimum pH 8.2. The cleavage products of actin by arginine esterase and trypsin were similar although trypsin activity was 5000-fold higher. Kallikrein produced a major fragment of actin not observed with arginine esterase and trypsin. It is concluded that arginine esterase has a low trypsin-like activity towards structural proteins and that this activity may have a physiological significance.
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PMID:Proteolytic activity of arginine esterase from dog seminal plasma towards actin and other structural proteins. Comparison with trypsin and kallikrein. 363 41

Kallikrein inhibiting proteins with two different molecular weight (6-8 X 10(4), 8-9 X 10(4) respectively) were observed in adrenalectomized rat kidney cortical soluble fraction. The larger one was observed in the kidneys of the adrenalectomized rats only when they had received chronic administration of excess amount of dexamethasone, and its kallikrein inhibitory activity was not lost with treatment with trypsin. This protein appears to be induced by chronic administration of glucocorticoid and might participate in the process of glucocorticoid regulating renal kallikrein kinin system.
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PMID:Endogenous kallikrein inhibitor in rat kidney cortex-effect of glucocorticoid administration. 364 17

Most previous studies have not significantly correlated urinary kallikrein to urinary kinins. We investigated whether urinary kininogen might influence kinin formation within the urine. On an ad-lib diet the 24 hour excretion of total and intact kininogen, kinins and kallikrein was determined in 24 control subjects, 20 untreated essential hypertensives, 12 with end-stage renal disease and 8 subjects with liver disease. Kallikrein and kinins were measured by a direct radioimmunoassay. Total kininogen was determined from the sum of preformed kinins and kinins generated after trypsin (intact kininogen). Cross reactivity between purified human low molecular weight kininogen and bradykinin antiserum was 3%. Total and intact kininogen were significantly correlated with kinins in controls, essential hypertension and liver disease. In essential hypertension, end-stage renal and liver diseases kinins were significantly decreased. This was associated with a reduction in kininogen but not kallikrein in essential hypertension and liver disease, and a reduction in kallikrein but not kininogen in end-stage renal disease. Thus, renal kinin generation in various states may be affected by either or both kininogen and kallikrein.
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PMID:Urinary kininogen: a possible regulator of kinin formation in normal individuals and subjects with essential hypertension, end-stage renal and liver disease. 381 87

The activation of Hageman factor in solid and fluid phase has been analyzed. Activation of highly purified Hageman factor occurred after it interacted with and became bound to a negatively charged surface. Activation was observed in the absence of enzymes that are inhibitable with diisopropylfluorophosphate, phenyl methyl sulfonyl fluoride and epsilon-amino-n-caproic acid. The binding of [(125)I]Hageman factor to the negatively charged surface was markedly inhibited by plasma or purified plasma proteins. Activation of Hageman factor in solution (fluid phase) was obtained with kallikrein, plasmin, and Factor XI (plasma thromboplastin antecedent). Kallikrein was greater than 10 times more active in its ability to activate Hageman factor than plasmin and Factor XI. The data offer a plausible explanation for the finding that highly purified kallikrein promotes clotting of normal plasma. In addition, the combined results of this and previously reported data from this laboratory indicate that the reciprocal activation of Hageman factor by kallikrein in fluid phase is essential for normal rate of activation of the intrinsic-clotting, kinin-forming, and fibrinolytic systems. Activation of Hageman factor was associated with three different structural changes in the molecule: (a) Purified Hageman factor, activated on negatively charged surfaces retained its native mol wt of 80-90,000. Presumably a conformational change accompanied activation. (b) In fluid phase, activation with kallikrein and plasmin did not result in cleavage of large fragments of rabbit Hageman factor, although the activation required hydrolytic capacity of the enzymes. (c) Activation of human Hageman factor with kallikrein or plasmin was associated with cleavage of the molecule to 52,000, 40,000, and 28,000 mol wt fragments. Activation of rabbit Hageman factor with trypsin resulted in cleavage of the molecule into three fragments, each of 30,000 mol wt as noted previously. This major cleavage occurred simultaneously with activation.
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PMID:Activation of Hageman factor in solid and fluid phases. A critical role of kallikrein. 427 29

1. The effect of age and androgen level on enzyme activity and cellular structure has been determined in the mouse submaxillary gland.2. A new protease which resembles chymotrypsin in its substrate specificity has been characterized in the gland.3. Activity of the chymotrypsin- and trypsin-like proteases and renin increased considerably in male mice concomitantly with proliferation of granules in the secretory tubules of the gland.4. The androgen dependence of the chymotrypsin- and trypsin-like enzymes, renin and the organelles within the secretory tubules was confirmed in castrated male mice. The activity of these enzymes increased and correlated with the appearance of intracellular granules in the secretory tubules when the castrated male mice and in addition female mice were treated with testosterone preparations.5. Kallikrein, a closely related protease, and amylase increased in activity with age but showed no sex-linked differences.6. The results suggest that kallikrein is sequestered in acinar cells whereas the androgen-dependent enzymes (chymotrypsin, trypsin and renin) are located in the secretory tubules.
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PMID:The influence of androgens on enzymes (chymotrypsin-and trypsin-like proteases, renin, kallikrein and amylase) and on cellular structure of the mouse submaxillary gland. 476 1

Kallikrein activatable by trypsin was found in the urine of normal rats, corresponding to about 33% of the total kallikrein excretion. This fraction was inhibited by aprotinin and kallikrein antiserum. There was no spontaneous activation at 20 degrees C for 24 h or at 37 degrees C for 15 h which indicates that the amount detectable in the urine may represent the levels of activatable kallikrein in the renal tubule. Sephacryl S-200 chromatography of the urine disclosed the presence of two forms of kallikrein, active and activatable, with apparent molecular weights of 30 000 and 34 500 respectively. These findings allow us to assume that the activatable fraction would correspond to prokallikrein, as described by others. In hypertensive one-kidney pole-ligated rats, the total urinary kallikrein did not differ from that excreted by solely uninephrectomized rats, though the active kallikrein showed a significant drop (P less than 0.001). These results suggest that in hypertensive rats there is an alteration in the activation mechanisms of kallikrein.
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PMID:Urinary excretion of activatable kallikrein in one-kidney pole-ligated hypertensive rats. 608 35


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