Plasmin Can Activate Plasma Prorenin but is Not Required for the Alkaline Phase of Acid Activation

1979 ◽  
Vol 57 (s5) ◽  
pp. 97s-99s ◽  
Author(s):  
Jean E. Sealey ◽  
S. A. Atlas ◽  
J. H. Laragh ◽  
M. Silverberg ◽  
A.P. Kaplan
Keyword(s):  
Plasma Kallikrein ◽  
Acid Activation ◽  
Plasminogen Activation ◽  
Alkaline Ph ◽  
Hageman Factor ◽  
Active Renin ◽  
Inactive Form ◽  
Free Plasma

1. Plasma prorenin is an inactive form of renin that is converted into active renin at alkaline pH in previously acidified plasma; this conversion of prorenin into renin is mediated by Hageman factor-dependent activation of prekallikrein, which, in turn, leads to prorenin activation. 2. Since plasma kallikrein can activate plasminogen, the present studies were designed to evaluate whether alkaline-phase activation of prorenin by plasma kallikrein is mediated via plasminogen activation. 3. We demonstrated that plasminogen is present in acid-treated plasma in sufficient quantity to convert prorenin into renin after activation by streptokinase. 4. However, alkaline-phase activation was completely normal in plasminogen-free plasma. 5. Therefore alkaline-phase activation of plasma prorenin is mediated by plasma kallikrein but is not dependent on kallikrein activation of plasminogen.

Activators of Inactive Renin (‘Prorenin’) in Human Plasma: Their Connection with Kinin Formation, Coagulation and Fibrinolysis

1979 ◽  
Vol 57 (s5) ◽  
pp. 89s-92s ◽  
Author(s):  
F. H. M. Derkx ◽  
B. N. Bouma ◽  
H. L. Tan-Tjiong ◽  
M. A. D. H. Schalekamp
Keyword(s):  
Human Plasma ◽  
Hageman Factor ◽  
Active Renin ◽  
Normal Plasma ◽  
Inactive Renin ◽  
Fletcher Factor ◽  
Free Plasma ◽  
Renin Activation ◽  
Dependent Pathway ◽  
Proteolytic Pathways

1. Human plasma was treated at 4°C with acid, trypsin, plasmin, streptokinase, urokinase, active Hageman factor fragment (β-XIIa) and β-XIIa-activated plasma prekallikrein (Fletcher factor). The conversion of inactive into active renin (activation) was studied in normal plasma (n = 10), Hageman factor-deficient plasma (n = 2), Fletcher factor-deficient plasma (n = 1) and plasminogen-free plasma (n = 4). 2. In normal plasma inactive renin was activated at pH 7·5 after treatment at pH < 4·0; at pH 3·3 the results were the same as with trypsin. This was also the case in plasminogen-free plasma. In Hageman factor-deficient plasma and in Fletcher factor-deficient plasma, however, the quantities of renin that were activated after acidification were much smaller than with trypsin. The addition of physiological amounts of active kallikrein to pH 3·3-pretreated Hageman factor-deficient plasma caused complete activation of renin. In contrast, the addition of active Hageman factor fragment to pH 3·3-pretreated Fletcher factor-deficient plasma had little or no effect. 3. Plasmin, streptokinase-activated plasminogen and urokinase-activated plasminogen activated inactive renin in pH 4·0-pretreated normal plasma as well as in pH 4·0-pretreated Hageman factor-deficient plasma and Fletcher factor-deficient plasma. 4. It is concluded that inactive renin is activated by two separate proteolytic pathways: one pathway depends on both Hageman factor and plasma prekallikrein, and the other pathway depends on plasminogen. In the Hageman factor-dependent pathway plasma kallikrein and not Hageman factor is the major activator of inactive renin. It is assumed that pH 3·3-treatment of plasma destroys the major inhibitors of kallikrein and that pH 4·0-treatment destroys the major inhibitor of plasmin.

THE MECHANISM OF THE ACID ACTIVATION OF RABBIT UTERINE RENIN

1979 ◽  
Vol 92 (4) ◽  
pp. 720-730 ◽  
Author(s):  
Jørgen Jørgensen
Keyword(s):  
Proteolytic Enzymes ◽  
Pressor Response ◽  
Gel Filtration ◽  
Acid Activation ◽  
Freezing And Thawing ◽  
Ph Optimum ◽  
Active Renin ◽  
Inactive Form ◽  
Repeated Freezing ◽  
Rate Of Activation

ABSTRACT Besides active renin an inactive form of renin could be demonstrated in uterine tissue. On gel filtration it was eluted as a molecule of slightly higher molecular weight than active renin, and it could be irreversibly activated by acidification at 37°C. The activation had a pH optimum between pH 3.8 and pH 5.3. Acid activated uterine renin was found identical to active uterine renin by 1) the formation of angiotensin I with time after addition of rat substrate, 2) the pressor response in the rat, 3) neutralization by antirenin and 4) similar Michaelian constants. Repeated freezing and thawing, acidification at 4°C and dialysis against 4 mol/l NaCl did not give any activation. A lower rate of activation of diluted samples and activation by trypsin at pH 7.4 suggest that proteolytic enzymes are involved in the activation.

scholarly journals RELEASE OF KALLIKREIN FROM GUINEA PIG LUNG DURING ANAPHYLAXIS

1966 ◽  
Vol 123 (3) ◽  
pp. 509-522 ◽  
Author(s):  
O. Jonasson ◽  
E. L. Becker
Keyword(s):  
Guinea Pig ◽  
Ellagic Acid ◽  
Proteolytic Enzyme ◽  
Molecular Size ◽  
Plasma Kallikrein ◽  
Hageman Factor ◽  
Reaction Proceeds ◽  
Perfused Lung ◽  
Antibody Reaction ◽  
Antigen Antibody

An antigen-antibody reaction occurring in the perfused sensitized guinea pig lung, has been demonstrated to release kallikrein, a proteolytic enzyme related to the formation of kinins. This lung kallikrein is similar to plasma kallikrein in all properties studied, including susceptibility to the same inhibitors, electrophoretic mobility, and heterogeneity in molecular size. The release of kallikrein during anaphylaxis in the guinea pig lung occurs in the presence of ethylenediaminetetraacetate. Perfusion of ellagic acid into nonsensitized lungs will also release kallikrein, presumably through activation of Hageman factor. On the basis of these findings the hypothesis is suggested that the kallikrein in perfused lung activated by the antigen-antibody reaction is, in fact, plasma kallikrein. It is further suggested that activation of such kallikrein by the antigen-antibody reaction proceeds through Hageman factor.

scholarly journals A comparison of the properties of renin isolated from pig and rat kidney

1976 ◽  
Vol 155 (2) ◽  
pp. 317-323 ◽  
Author(s):  
M Lauritzen ◽  
J J Damsgaard ◽  
I Rubin ◽  
E Lauritzen
Keyword(s):  
Isoelectric Focusing ◽  
Rat Kidney ◽  
Substrate Affinity ◽  
Acid Activation ◽  
Renin Substrate ◽  
Crossed Immunoelectrophoresis ◽  
Inactive Form ◽  
Isoelectric Points ◽  
Michaelis Constants ◽  
Rat Kidneys

1. On isoelectric focusing, renin from rat kidneys showed three activity peaks with pI values at pH 5.0, 5.2 and 5.4 after a purification procedure involving differential centrifugation, acidification, chromatography on Sephadex G-75 and dialysis. 2. The preparation (purified 140-fold) was compared with a crude kidney extract in the absence and presence of 3 M-urea by isoelectric focusing. The pattern of activity distribution was confirmed by these experiments and the content of isoenzymes in the three groups calculated. 3. Pig renin was prepared and compared with rat renin with regard to molecular weight, acid activation, behaviour on isoelectric focusing, immunogenicity and substrate affinity. 4. Extracts of rat kidney contained multiple forms of renin with mol.wt. between 39000and 42000, whereas active pig renin had an approximate mol.wt. of 40000. Acidification of rat renal extracts did not increase the activity of renin, indicating the absence of an inactive form of renin in rat kidneys, whereas pig renin was activated by this procedure. Pig renin has isoelectric points at pH 4.6, 4.8, 5.05 and 5.2, significantly lower than for rat renin. The isoenzymes from the two species had no antigenicity in common, as shown by crossed immunoelectrophoresis or rocket immunoelectrophoresis. 5. The Michaelis constants for pig and rat renin were in the same range, 1 × 10(-6) M, when rat renin substrate was used. The relative content of rat isoenzyme with pI in the pH ranges 4.9-5.1, 5.1-5.3 and 5.3-5.5 was approx. 20, 27 and 53% respectively. Purified pig renin prepared in two different ways had isoenzymes with pI in the pH regions 4.5-4.7, 4.7-4.9, 4.9-5.05 and 5.05-5.20 in the approximate proportions 14, 24, 28 and 29%.

Bovine Hageman Factor: Physicochemical Properties and Mechanism of Activation

1975 ◽  
Author(s):  
A. Molla ◽  
H. Claeys ◽  
D. Collen
Keyword(s):  
Conformational Changes ◽  
Analytical Ultracentrifugation ◽  
Specific Activity ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sedimentation Coefficient ◽  
Factor Xii ◽  
Hageman Factor ◽  
Terminal Residue ◽  
Inactive Form ◽  
Fresh Plasma

Bovine Hageman factor (factor XII) was obtained in inactive form from fresh plasma with a recovery of 54.7±9.0 per cent and a yield of 16.3±2.9 mg per liter. The specific activity after activation with kaolin, determined with Hageman factor deficient human plasma, was 35.6±2.6 units (the activity of 1 ml fresh BaSO4-adsorbed bovine plasma) per mg protein.Analytical ultracentrifugation revealed a homogeneous protein with a sedimentation coefficient of 4.36. The extinction coefficient (A280 nm %) was 14.4, and the NH2-terminal residue Ala (0.6 mole/mole determined as Dns-Ala). SDS-polyacrylamide gel electrophoresis (PAGE) in the presence of dithiothreitol revealed a doublet with an average estimated mol wt of 76,000 and a difference of less than 5,000 between the two forms. Chemical analysis revealed (in moles per mole) Met: 2; His: 59; Lys: 28; Arg: 32 and sialic acid: 13 (thio-barbituric acid assay), hexose: 26 (orcinol method). PAGE at pH 2.5 revealed two and PAGE at pH 8.3 six main bands.Over 90 per cent of the purified iodine-labeled protein was adsorbed on celite. About 95 per cent of the enzyme activity was destroyed by incubation with 10−2 M di-iso-propylfluorophosphate (DFP) for 24 hr at room temperature. Between 65 and 85 per cent of the protein was eluted from the celite with 5% SDS. Both the NH2-terminal residue and the mol wt of the eluted protein were unchanged suggesting that activation of the proenzyme is the result of conformational changes with exposure of an active center serine residue. Measurements of radioactive DFP incorporation and COOH-terminal analysis, to prove this hypothesis are in progress.

scholarly journals Structure of BbKI, a disulfide-free plasma kallikrein inhibitor

2015 ◽  
Vol 71 (8) ◽  
pp. 1055-1062 ◽  
Author(s):  
Dongwen Zhou ◽  
Daiane Hansen ◽  
Ivan G. Shabalin ◽  
Alla Gustchina ◽  
Debora F. Vieira ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Potent Inhibitor ◽  
Tight Binding ◽  
Plasma Kallikrein ◽  
Excessive Bleeding ◽  
Antithrombotic Activity ◽  
Plant Seeds ◽  
The Family ◽  
Free Plasma ◽  
Kunitz Family

A serine protease inhibitor fromBauhinia bauhinioides(BbKI) belongs to the Kunitz family of plant inhibitors, which are common in plant seeds. BbKI does not contain any disulfides, unlike most other members of this family. It is a potent inhibitor of plasma kallikrein, in addition to other serine proteases, and thus exhibits antithrombotic activity. A high-resolution crystal structure of recombinantly expressed BbKI was determined (at 1.4 Å resolution) and was compared with the structures of other members of the family. Modeling of a complex of BbKI with plasma kallikrein indicates that changes in the local structure of the reactive loop that includes the specificity-determining Arg64 are necessary in order to explain the tight binding. An R64A mutant of BbKI was found to be a weaker inhibitor of plasma kallikrein, but was much more potent against plasmin, suggesting that this mutant may be useful for preventing the breakup of fibrin and maintaining clot stability, thus preventing excessive bleeding.

Activation of bovine factor XII (Hageman factor) by plasma kallikrein

Biochemistry ◽  
1980 ◽  
Vol 19 (7) ◽  
pp. 1322-1330 ◽  
Author(s):  
Kazuo Fujikawa ◽  
Ronald L. Heimark ◽  
Kotoku Kurachi ◽  
Earl W. Davie
Keyword(s):  
Plasma Kallikrein ◽  
Factor Xii ◽  
Hageman Factor ◽  
Bovine Factor

Effects of t-AMCHA and EACA on the Plasma Kallikrein System

1977 ◽  
Vol 37 (01) ◽  
pp. 104-110 ◽  
Author(s):  
Masao Nakahara
Keyword(s):  
Trypsin Inhibitor ◽  
Gel Filtration ◽  
Lima Bean ◽  
Inhibitory Influence ◽  
Plasma Kallikrein ◽  
Hageman Factor ◽  
Dog Plasma ◽  
Bean Trypsin Inhibitor ◽  
Kinin Level ◽  
Esterase Activities

SummaryVaried amounts of t-AMCHA or EACA added to non-contact fresh dog plasma generates kininogenase and TAME esterase activities. These phenomena may be abolished by prior addition of lima bean trypsin inhibitor. t-AMCHA or EACA had no effect on partially purified kallikrein, but had a significant inhibitory influence on plasma kininase. The generation of prekallikrein activator with t-AMCHA was ascertained by gel filtration on a Sephadex G-100 column. The blood kinin level increased about 50% one hr after administration of t-AMCHA. It is suggested from these results that t-AMCHA may initiate the true activation of the kallikrein system by activating the Hageman factor.

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