Renin Precursor Synthesis and Renin-Binding Proteins in the Mouse

1979 ◽  
Vol 57 (s5) ◽  
pp. 109s-110s ◽  
Author(s):  
K. Poulsen
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Plasma Proteins ◽  
Tertiary Structure ◽  
Submaxillary Gland ◽  
Α2 Macroglobulin ◽  
Precursor Synthesis ◽  
Predominant Form ◽  
Molecular Nature

1. The precursor synthesis of renin, the storage form in the kidney and the submaxillary gland, and the molecular nature of the forms in plasma were studied in the mouse. 2. Renin is synthesized as a precursor (pre-prorenin) with a molecular weight of 50 000. 3. Renin is stored in the submaxillary gland and the kidneys as fully active renin with a molecular weight of 40 000. 4. The predominant form of renin in plasma is the active mol. wt. 40 000 form. High-molecular-weight forms of renin (800 000 and 70 000) are also present in plasma. 5. Pure 125I-labelled mol. wt. 40 000 renin binds, after a change in the tertiary structure, to the plasma protease inhibitors α2-macroglobulin, inter-α-trypsin inhibitor and α2-antithrombin. It binds also to lipoprotein and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins. 6. The high-molecular-weight forms of renin in plasma may be complexes of renin with plasma protease inhibitors and lipoprotein.

Is High-Molecular-Weight-Renin Binding of Renin to the Protease Inhibitors and Lipoproteins?

1978 ◽  
Vol 55 (s4) ◽  
pp. 125s-128s
Author(s):  
K. Poulsen ◽  
A. H. Nielsen ◽  
S. Lykkegaard ◽  
C. Malling ◽  
J. Krøll ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Plasma Proteins ◽  
Tertiary Structure ◽  
Limited Proteolysis ◽  
Submaxillary Gland ◽  
Enzymic Activity ◽  
Molecular Weights ◽  
Α2 Macroglobulin

1. Two high-molecular-weight forms of renin (molecular weights 800 000 and 70 000) are present in mouse plasma. 2. The 800 000 form could be activated and converted into the fully active 40 000 form, by acid or limited proteolysis. The 70 000 form was activated without change in molecular weight. 3. In addition to its enzymic activity, renin was measured by a direct radioimmunoassay, which revealed that the current acid treatment of plasma did not activate all the renin present. 4. Renin is stored as fully active 40 000 renin, with a specific enzymic reactivity of 0·4 × 10−3 GU ng−1, in the submaxillary gland of mice. 5. Pure 125I-labelled 40 000 submaxillary renin did not bind to plasma proteins. However, by changing the tertiary structure of renin, it was bound to some of the plasma protease inhibitors; α2-macroglobulin, inter-α-trypsin inhibitor and α2-antithrombin. It was also bound to α1- and β1-lipoprotein, albumin and an unidentified plasma protein. No binding was seen to more than 50 other studied plasma proteins.

The Kinetics Of The Inhibition Of Human Plasma Kallikrein By Plasma Protease Inhibitors: Role Of High Molecular Weight Kininogen

1981 ◽  
Author(s):  
M Schapira ◽  
A James ◽  
C F Scott ◽  
F Kueppers ◽  
H L James ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Substrate Inhibition ◽  
Catalytic Efficiency ◽  
Reaction Rates ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen ◽  
Α2 Macroglobulin ◽  
Competitive Inhibitors

Plasma kallikrein (KAL) is inhibited by several plasma protease inhibitors, including C1-inhibitor (C1-INH), antithrombin III (ATIII), α1-antitrypsin (α1AT), and α2-macroglobulin (α2M). To assess the mechanism of action and the relative importance of these inhibitors, we have undertaken inhibition studies with purified proteins, using H-D-Pro- Phe-Arg-Nan as KAL substrate. Inhibition was competitive with C1INH, ATIII, and α1AT and noncompetitive with α2M. KAL retained 14% of its catalytic efficiency when complexed to α2M. The rate constants for inhibition by C1INH, ATIII, α1AT, and α2M were 28, 0.18, 0.003, and 6.9 M-ls-1(10-3) respectively. Michaelis-Menten kinetics was observed for the inhibition by ATIII, αlAT, and α2M. The constants for the rate-limiting formation of the irreversible complexes were 16, 0.27 and 2.0 s-1(xl02), while the KI’s for the reversible complex were 86, 63, and 0.29 γM, respectively for ATIII, α1AT and α2M. In_contrast, no Michaelis-Menten complex was observed when C1INH inhibited KAL. These results indicate that (a) C1INH is the most efficient inhibitor of KAL, (b) α2M is a significant inhibitor of KAL, (c) both ATIII and αlAT are probably not significant inhibitors of KAL. We have shown that high molecular weight kininogen (HMWK) decreases the inactivation rate of KAL by C1INH by forming a reversible complex with KAL. We now report that the reaction rates of KAL with ATIII and α1AT, which are competitive inhibitors, were decreased by 50%, when HMWK was 1 U/ml or 0.73 γM. When KAL was inhibited by α2M, a noncompetitive inhibitor, the inactivation rates were identical in the presence or absence of HMWK. Since HMWK protects KAL from being inhibited by competitive inhibitors but not by a noncompetitive one, these results confirm our previous observation indicating that the binding site for IMWK on KAL is closely linked to its catalytic site.

Soluble Fibrin Complexes and Fibrinogen Heterogeneity in Diabetes mellitus

1980 ◽  
Vol 44 (03) ◽  
pp. 130-134 ◽  
Author(s):  
E B Tsianos ◽  
N E Stathakis
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Plasma Proteins ◽  
Polyacrylamide Gel Electrophoresis ◽  
Gel Filtration ◽  
Lower Molecular Weight ◽  
Polyacrylamide Gels ◽  
Soluble Fibrin ◽  
Α2 Macroglobulin ◽  
Patients With Diabetes

SummaryThe presence of soluble fibrin complexes (SFC) measured by gel filtration of plasma on 4% agarose columns, fibrinogen heterogeneity on 3.5% SDS-polyacrylamide gels and the concentrations of several plasma proteins were evaluated in 39 patients with diabetes mellitus (DM) and 19 matched control subjects. A small but significant increase of SFC was found in DM (p<0.01). On individual basis 51.2% of the patients had increased SFC (>M + 2 SD of the controls). Polyacrylamide gel electrophoresis of the SFC showed no evidence of cross-linking or proteolysis. Plasma clots formed in the presence of EDTA and trasylol were analysed in SDS-polyacrylamide gels in a normal and two lower molecular weight fibrin bands (band I, II, III). The percentage of band I fibrinogen was in diabetics (65.3 ± 4.7%) lower than that of the controls (71.8 ± 4.5%) (p < 0.01). Fibrinogen levels, antithrombin III, α1-antitrypsin, α2-macroglobulin and plasminogen were significantly increased in DM. We suggest that in DM there is an enhancement of intravascular fibrin formation and accelerated fibrinogen degradation to lower molecular weight forms.

The Contact Phase of Blood Coagulation in Diabetes Mellitus and in Patients with Vasculopathy

1984 ◽  
Vol 52 (03) ◽  
pp. 221-223 ◽  
Author(s):  
M Christe ◽  
P Gattlen ◽  
J Fritschi ◽  
B Lämmle ◽  
W Berger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Weight ◽  
Blood Coagulation ◽  
High Molecular Weight ◽  
Negative Correlation ◽  
Factor Xii ◽  
C1 Inhibitor ◽  
High Molecular Weight Kininogen ◽  
Contact Phase ◽  
Α2 Macroglobulin

SummaryThe contact phase has been studied in diabetics and patients with macroangiopathy. Factor XII and high molecular weight kininogen (HMWK) are normal. C1-inhibitor and also α2-macroglobulin are significantly elevated in diabetics with complications, for α1-macroglobulin especially in patients with nephropathy, 137.5% ± 36.0 (p <0.001). C1-inhibitor is also increased in vasculopathy without diabetes 113.2 ± 22.1 (p <0.01).Prekallikrein (PK) is increased in all patients’ groups (Table 2) as compared to normals. PK is particularly high (134% ± 32) in 5 diabetics without macroangiopathy but with sensomotor neuropathy. This difference is remarkable because of the older age of diabetics and the negative correlation of PK with age in normals.

Homocysteinylation score of high-molecular weight plasma proteins

Amino Acids ◽  
2013 ◽  
Vol 46 (4) ◽  
pp. 893-899 ◽  
Author(s):  
Alexandr A. Zhloba ◽  
Tatiana F. Subbotina
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Plasma Proteins

Gene Expression of the High Molecular Weight Proteinase Inhibitor α2-Macroglobulin

1992 ◽  
Vol 373 (2) ◽  
pp. 509-516 ◽  
Author(s):  
EVA KRAUSE ◽  
URSULA WEGENKA ◽  
GARSTEN MÖLLER ◽  
FRIEDEMANN HORN ◽  
PETER C. HEINRICH
Keyword(s):  
Gene Expression ◽  
Molecular Weight ◽  
High Molecular Weight ◽  
Proteinase Inhibitor ◽  
Α2 Macroglobulin

Role of proteolysis in apoptosis: involvement of serine proteases in internucleosomal DNA fragmentation in immature thymocytes

1993 ◽  
Vol 71 (9-10) ◽  
pp. 488-500 ◽  
Author(s):  
Valerie M. Weaver ◽  
Boleslaw Lach ◽  
P. Roy Walker ◽  
Marianna Sikorska
Keyword(s):  
Molecular Weight ◽  
Serine Protease ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Dna Fragmentation ◽  
Dna Cleavage ◽  
Apoptotic Cell ◽  
Dependent Manner ◽  
Serine Protease Inhibitors ◽  
High Molecular Weight Dna

Three chemically distinct serine, but not cysteine, protease inhibitors (phenylmethylsulphonyl fluoride, N-tosyl-L-phenylalanylchloromethyl ketone and 3,4-dichloroisocoumarin) prevented, in a dose-dependent manner, the characteristic apoptotic internucleosomal DNA cleavage (DNA ladder) typically observed in thymocytes in response to dexamethasone and teniposide VM-26. This effect was not the result of a direct inhibition of the Ca2+, Mg2+-dependent endonuclease, since oligonucleosomal DNA cleavage occurred in the presence of these inhibitors in isolated nuclei. The proteolytic step occurred at a very early stage of apoptosis, and preincubation of thymocytes with the inhibitors before dexamethasone or teniposide VM-26 were added irreversibly suppressed ladder formation. This implied that the cellular effector(s) of these compounds preexisted and were not resynthesized in response to the inducers of apoptosis. Serine protease inhibitors also suppressed apoptotic cell shrinkage and complete nuclear collapse, suggesting that these morphological changes were directly related to internucleosomal fragmentation of DNA. However, the serine protease inhibitors did not prevent high molecular weight DNA cleavage (> 50 kilobases) that preceded the ladder formation and thymocytes still died by apoptosis. This supported the view that internucleosomal DNA cleavage, considered to be the biochemical marker of apoptosis, might in fact be a late and dispensable step and that the newly described high molecular weight DNA cleavage might be a better indicator of apoptosis.Key words: serine protease, apoptosis, internucleosomal DNA fragmentation, high molecular weight DNA cleavage, protease inhibitors.

scholarly journals High Molecular Weight (HMW): total adiponectin ratio is low in hiv-infected women receiving protease inhibitors

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Fierdoz Omar ◽  
Joel A Dave ◽  
Judy A King ◽  
Naomi S Levitt ◽  
Tahir S Pillay
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Total Adiponectin

Corrections - High Molecular Weight Kininogen or its Light Chain Protects Human Plasma Kallikrein from Inactivation by Plasma Protease Inhibitors

Biochemistry ◽  
1982 ◽  
Vol 21 (12) ◽  
pp. 3036-3036
Author(s):  
Marc Schapira ◽  
Cheryl Scott ◽  
Ann James ◽  
Lee Silver ◽  
Frederich Kueppers ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Human Plasma ◽  
High Molecular Weight ◽  
Protease Inhibitors ◽  
Light Chain ◽  
Plasma Kallikrein ◽  
High Molecular Weight Kininogen

scholarly journals Inactivation of α2-Macroglobulin by Activated Human Polymorphonuclear Leukocytes

1994 ◽  
Vol 3 (2) ◽  
pp. 117-123 ◽  
Author(s):  
G. Deby-Dupont ◽  
J.-L. Croisier ◽  
G. Camus ◽  
D. Brumioul ◽  
M. Mathy-Hartert ◽  
...  
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Proteolytic Activity ◽  
Polymorphonuclear Leukocytes ◽  
Cytochalasin B ◽  
Hypochlorous Acid ◽  
Myeloperoxidase Activity ◽  
Trypsin Activity ◽  
Α2 Macroglobulin ◽  
Human Polymorphonuclear Leukocytes

The proteolytic activity of trypsin releases the dye Remazol Brilliant Blue from its high molecular weight substrate, the skin powder (Hide Powder Azure, Sigma), with an increase in absorbance at 595 nm. Active α2- macroglobulin (80 μg/ml) totally inhibits the proteolytic activity of trypsin (14 μg/ml) by trapping this protease. But after a 20 min incubation of α2-macroglobulin at 37°C with 2 × 106human polymorphonuclear leukocytes activated by N-formyl-L-methionyl-L-leucyl-L-phenylalanine (10−7M) and cytochalasin B (10−8M), 100% of trypsin activity was recovered, indicating a total inactivation of α2-macroglobuHn. Incubation with granulocyte myeloperoxidase also inactivates α2-macroglobulin. Hypochlorous acid, a by-product of myeloperoxidase activity, at a concentration of 10−7M also inactivates α2-macroglobulin, which indicates that an important cause of α2-macroglobulin inactivation by activated polymorphonuclear leukocytes could be the activity of myeloperoxidase.

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