Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.73 (urokinase-type plasminogen activator)
 10,685 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Further evidence is presented that the acrosomal proteinase acrosin exists as a zymogen precursor in freshly ejaculated boar spermatozoa. Autoactivation of proacrosin to acrosin takes place optimally at slightly alkaline pH and in the presence of calcium ions. Activation is considerably accelerated by catalytic amounts of trypsin or highly purified acrosin. A significant acceleration of the activation is also achieved by porcine pancreatic and urinary kallikrein, whereas chymotrypsin, plasmin, thrombin or urokinase showed no effect. Activation can be inhibited by p-amino-benzamidine and p-nitrophenyl p'-guanidino-benzoate. Electrophoretic analysis at different stages of activation revealed that during this process various molecular forms of acrosin are produced, apparently by limited proteolysis.
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PMID:Multiple forms of boar acrosin and their relationship to proenzyme activation. 0 66

Skin fibroblasts from patients with inherited adenomatosis of the large bowel (ACR-SF) possess alterations in actin microfilament (MF) organization which serve to distinguish "predisposed" cells from fibroblasts derived from normal individuals (NSF). MF bundle frequency and diameter were considerably reduced in ACR-SF compared to NSF. This deficit in MF density correlated with a 60% decline in cytoskeletal-associated actin half-life. Absence of a well-structured MF network in ACR-SF was reflected in relatively poor cell-to-substrate adhesion (as indicated by increased sensitivity to trypsin release) and extensive membrane ruffling. Unlike NSF, ACR-SF failed to develop well-defined vinculin-containing focal contacts although the cellular content of vinculin was approximately the same in both cell types. The relatively low substrate adhesivity and reduced incidence of adhesive structures (i.e., MF and associated focal contacts) which typify ACR-SF correlated with a sixfold increase in cellular plasminogen activator (PA) activity. This increased protease activity corresponded with a 50-70% reduction in the content of the PA inhibitor-like protein p50 in both the saponin-resistant undersurface matrix and the culture medium. Increased motility and reduced cell-to-substrate adhesion, involving several cellular structural elements, appear to be significant correlates of the "predisposed" phenotype in cultured fibroblasts.
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PMID:Analysis of actin microfilaments and cell-to-substrate adhesive structures in human fibroblasts from individuals genetically predisposed to colonic carcinoma. 207 Aug 20

A number of esters of p-guanidinobenzoic acid have been synthesized which contain a glycolyl peptide as the departing group. In the case of several enzymes such as trypsin and plasma kallikrein, depsipeptides were obtained which were considerably more reactive than the ethyl ester in inactivation of the protease by acyl-enzyme formation; the depsipeptide processing -CH2CO-Phe-NH2 as a leaving group displayed the highest reactivity. They were less effective in the case of urokinase, plasmin, and urinary kallikrein. Boar acrosin was very susceptible to inactivation by both ethyl and peptidyl esters. Depsipeptides possessing a longer peptide chain and a secondary carbon as a leaving group showed lower activities. The results demonstrate the productive use of the departing group region of protease active centers to obtain selectivity.
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PMID:Inactivation of trypsin-like proteases by depsipeptides of p-guanidinobenzoic acid. 645 82

Human seminal plasma trypsin-like proteinase inhibitor (HSTPI) was separated and examined by trypsin Cellulofine affinity adsorption and Cellulofine GCL-300 gel filtration and its inhibitory action toward some arginine amidases obtained from the urine, semen, and blood of humans. HSTPI showed strong inhibitory action toward two types of human seminal plasma basic arginine amidases (BHSAA-L and -A), human seminal plasma acidic arginine amidase with affinity to lima bean trypsin inhibitor (LBTI) column (AHSAA-L), and human acrosin and thrombin. Conversely, no or little inhibition was observed toward human urinary arginine amidase-2, human high molecular weight urokinase, or human seminal plasma acidic arginine amidase with affinity to aprotinin column (AHSAA-A, tissue kallikrein). Measurement of Ki values of BHSAA-L with affinity to LBTI column toward HSTPI and LBTI revealed that the arginine amidase had a stronger affinity for LBTI than that for HSTPI. This indicates that it is the difference in Ki values that allows BHSAA-L to be separated by the LBTI affinity adsorption method from human seminal plasma containing a large amount of HSTPI.
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PMID:Human seminal plasma proteinase inhibitor: action toward some trypsin-like arginine amidases from humans. 837 82

Protein C inhibitor (PCI) is a nonspecific, heparin-binding serpin (serine protease inhibitor) that inactivates many plasmatic and extravascular serine proteases by forming stable 1:1 complexes. Proteases inhibited by PCI include the anticoagulant activated protein C, the plasminogen activator urokinase, and the sperm protease acrosin. In humans PCI circulates as a plasma protein but is also present at high concentrations in organs of the male reproductive tract. The biological role of PCI has not been defined so far. However, the colocalization of high concentrations of PCI together with several of its target proteases in the male reproductive tract suggests a role of PCI in reproduction. We generated mice lacking PCI by homologous recombination. Here we show that PCI(-/-) mice are apparently healthy but that males of this genotype are infertile. Infertility was apparently caused by abnormal spermatogenesis due to destruction of the Sertoli cell barrier, perhaps due to unopposed proteolytic activity. The resulting sperm are malformed and are morphologically similar to abnormal sperm seen in some cases of human male infertility. This animal model might therefore be useful for analyzing the molecular bases of these human conditions.
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PMID:Disruption of the protein C inhibitor gene results in impaired spermatogenesis and male infertility. 1112 Jul 60

The effect of tannic acid, a common flavonoid, on the acrosin and plasminogen activator activity and plasmin activity of human and ram spermatozoa was evaluated. Acrosin and plasminogen activator activity were determined by spectrophotometry using the chromogenic substrates N-alpha-benzoyl-DL-arginine para-nitroanilide-HCl (BAPNA) and H-D-valyl-L-leucyl-L-lysine-p-nitroanilide-2HCl (S-2251), respectively. In extracts from both human and ovine acrosomes, the activities of acrosin and plasminogen activators were susceptible to tannic acid inhibition. The inhibitory effect of tannic acid was observed at concentrations > 50 micromol l(-1) in a dose-dependent manner. In additional experiments, low concentrations of tannic acid significantly inhibited tissue-type plasminogen activator, urokinase-type plasminogen activator and plasmin activity in a concentration-dependent manner over the range 0.25-200 micromol l(-1). Tannic acid reduced the motility of ram spermatozoa at a concentration of 1000 micromol l(-1) after 2 and 3 h co-incubation with spermatozoa. The motility of human spermatozoa remained unchanged over the range 0.1-1000 micromol tannic acid l(-1) during 3 h co-incubation. These results indicate that tannic acid inhibited the activity of both acrosin and plasminogen activator and indicates a possible mechanism by which flavonoids exert their antifertility effects.
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PMID:Inhibition of human and ovine acrosomal enzymes by tannic acid in vitro. 1122 36

Many serine proteases play important regulatory roles in complex biological systems, but only a few have been linked directly with capillary morphogenesis and angiogenesis. Here we provide evidence that serine protease activities, independent of the plasminogen activation cascade, are required for microvascular endothelial cell reorganization and capillary morphogenesis in vitro. A homology cloning approach targeting conserved motifs present in all serine proteases, was used to identify candidate serine proteases involved in these processes, and revealed 5 genes (acrosin, testisin, neurosin, PSP and neurotrypsin), none of which had been associated previously with expression in endothelial cells. A subsequent gene-specific RT-PCR screen for 22 serine proteases confirmed expression of these 5 genes and identified 7 additional serine protease genes expressed by human endothelial cells, urokinase-type plasminogen activator, protein C, TMPRSS2, hepsin, matriptase/MT-SP1, dipeptidylpeptidase IV, and seprase. Differences in serine protease gene expression between microvascular and human umbilical vein endothelial cells (HUVECs) were identified and several serine protease genes were found to be regulated by the nature of the substratum, ie. artificial basement membrane or fibrillar type I collagen. mRNA transcripts of several serine protease genes were associated with blood vessels in vivo by in situ hybridization of human tissue specimens. These data suggest a potential role for serine proteases, not previously associated with endothelium, in vascular function and angiogenesis.
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PMID:Endothelial cell serine proteases expressed during vascular morphogenesis and angiogenesis. 1262 42