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

---

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

Mechanisms were studied that might explain the attachment and damage to Candida albicans pseudohyphae by neutrophils in the absence of serum. Attachment of neutrophils to pseudo hyphae was inhibited by Candida mannans (1-10 mg/ml), but not by mannose, dextran, chitin, conconavalin A, or highly charged polyamino acids. Contact was also inhibited by pretreatment of Candida before incubation with neutrophils with chymotrypsin, but not trypsin or several inhibitors of proteases. Similar results were obtained with pretreatment of neutrophils, except that trypsin was inhibitory. When pseudohyphae were killed with ultraviolet light, proteinpolysaccharide complexes of mol wt <10,000 were released which appeared to bind to the surfaces of neutrophils and inhibit contact between neutrophils and Candida, as well as other fungi. Damage to Candida by neutrophils was inhibited by agents known to act on neutrophil oxidative microbicidal mechanisms, including sodium cyanide, sodium azide, catalase, superoxide dismutase, and 1, 4 diazobicyclo (2, 2, 2) octane, a singlet oxygen quencher. Neutrophils from a patient with chronic granulomatous disease did not damage Candida at all. However, the hydroxyl radical scavengers mannitol and benzoate were not inhibitory. Cationic proteins and lactoferrin also did not appear to play a major role in this system. Low concentrations of lysozyme which did not damage Candida in isotonic buffer solutions damaged pseudohyphae in distilled water. Isolated neutrophil granules damaged pseudohyphae only with added hydrogen peroxide and halide, and damage occurred only with granule fractions known to contain myeloperoxidase. These findings suggest that neutrophils recognized a molecule on the Candida surface which has a chymotrypsin sensitive protein component, and which may be liberated from the cell surface upon death of organism. The neutrophil receptors for Candida appear to be sensitive to trypsin and chymotrypsin. Damage to Candida by neutrophils occurred primarily by oxidative mechanisms, including the production of superoxide and hydrogen peroxide interacting with myeloperoxidase and halide, as well as singlet oxygen, but did not appear to involve hydroxyl radical. Lysozyme might have an accessory role, under some conditions.
...
PMID:Mechanisms of attachment of neutrophils to Candida albicans pseudohyphae in the absence of serum, and of subsequent damage to pseudohyphae by microbicidal processes of neutrophils in vitro. 34 Apr 71

1. The serum proteinase inhibitors alpha 1-antitrypsin, alpha 2-macroglobulin, inter-alpha-trypsin inhibitor and C1-esterase inhibitor were found not to affect the catalytic activity of human enterokinase, whereas bovine trypsin activity was modified essentially as expected. Enterokinase was also not inhibited by Trasylol (trypsin inhibitor from bovine lung) or bovine pancreatic trypsin inhibitor. No other component in human or mouse serum complexing with enterokinase was identified. 2. Human enterokinase administered intravenously into mice was rapidly cleared from the circulation with a half-life of 2.5 min. This removal was not the result of the difference in species, since partially purified mouse enterokinase was cleared at the same rate as the human enzyme. Clearance was mediated by recognition of the carbohydrate portion of enterokinase and not through specific recognition of its catalytic site. Immunofluorescent staining showed that the enzyme accumulated in the liver. Attempts to block the clearance by the simultaneous infusion of competing glycoproteins suggested that enterokinase was taken up by hepatocytes. Of the glycoproteins tested only two, human lactoferrin (terminal fucosyl alpha 1 leads to 3 N-acetylglucosamine) and bovine asialo-fetuin (terminal galactosyl beta 1 leads to 4 N-acetylglucosamine) were weakly competitive. Two inhibitors of endocytosis, Intralipid and Triton WR1339, failed to delay the removal of enterokinase. It is proposed that enterokinase is cleared from the circulation by an as yet uncharacterized hepatocyte receptor.
...
PMID:Identification of a defence mechanism in vivo against the leakage of enterokinase into the blood. 39 51

Levels of immunoreactive trypsin were measured in pure pancreatic juice obtained endoscopically from 44 patients with suspected pancreatic disease. Patients with pancreatic cancer all had low trypsin concentrations (median 3.6 micrograms/ml, range 0.6--12.0), but those with chronic pancreatitis had very variable levels (median 14.2 micrograms/ml, range 3.2--76.8), showing a considerable overlap with patients without pancreatic disease (median 37.1 micrograms/ml, range 10.4--66.0). When levels of lactoferrin in pancreatic juice were measured, all patients with chronic pancreatitis were found to have much higher levels (all greater than 900 ng/ml) than control subjects or patients with pancreatic cancer (all less than 400 ng/ml). The combined measurement of trypsin and lactoferrin in pure pancreatic juice appeared to be more promising than any other currently available test for the separation of patients with pancreatic cancer from those with chronic pancreatitis.
...
PMID:Trypsin and lactoferrin levels in pure pancreatic juice in patients with pancreatic disease. 52 74

The effect of trypsin and chymotrypsin on antibacterial factors in bovine colostrum has been studied. Endogenous complement in colostrum was extremely sensitive to both enzymes. IgM was attacked by chymotrypsin but not by trypsin. Trypsin slowly attacked IgG1, causing loss of biological activity due to cleavage of both light and heavy chains. IgG1 was only very slightly attacked by chymotrypsin. Lactoferrin and transferrin in the iron-free state were both susceptible to proteolysis, but the iron saturated forms were more resistant and tended to give rise to stable iron-binding fragments.
...
PMID:The effect of trypsin and chymotrypsin on the antibacterial activity of complement, antibodies, and lactoferrin and transferrin in bovine colostrum. 74 24

The iron-saturated and iron-free (apo) forms of bovine transferrin and lactoferrin were digested with trypsin and the digests analysed by column chromatography and electrophoresis. Both of the iron-saturated proteins were more resistant to proteolysis than the corresponding apoproteins, and iron-transferrin was more resistant than iron-lactoferrin. Digestion of iron-transferrin yielded two iron-binding fragments with molecular weights of 32 000 and 38 500 whereas apotransferrin yielded only the larger fragment. In digests of lactoferrin, up to five different fragments with molecular weights ranging from 25 000 to 52 700 were detected, there being no obvious qualitative difference between digests of iron-lactoferrin and apolactoferrin. The susceptibility of apolactoferrin to tryptic digestion was only slightly reduced when apolactoferrin was complexed with beta-lactoglobulin, suggesting that complex-formation is not a mechanism for protecting lactoferrin against intestinal degradation. There was no immunological cross reaction between bovine transferrin or its digestion products against anti-lactoferrin antiserum, or vice-versa.
...
PMID:The effect of trypsin on bovine transferrin and lactoferrin. 97 13

In vivo most extracellular iron is bound to transferrin or lactoferrin in such a way as to be unable to catalyze the formation of hydroxyl radical from superoxide (.O2-) and hydrogen peroxide (H2O2). At sites of Pseudomonas aeruginosa infection bacterial and neutrophil products could possibly modify transferrin and/or lactoferrin forming catalytic iron complexes. To examine this possibility, diferrictransferrin and diferriclactoferrin which had been incubated with pseudomonas elastase, pseudomonas alkaline protease, human neutrophil elastase, trypsin, or the myeloperoxidase product HOCl were added to a hypoxanthine/xanthine oxidase .O2-/H2O2 generating system. Hydroxyl radical formation was only detected with pseudomonas elastase treated diferrictransferrin and, to a much lesser extent, diferriclactoferrin. This effect was enhanced by the combination of pseudomonas elastase with other proteases, most prominently neutrophil elastase. Addition of pseudomonas elastase-treated diferrictransferrin to stimulated neutrophils also resulted in hydroxyl radical generation. Incubation of pseudomonas elastase with transferrin which had been selectively iron loaded at either the NH2- or COOH-terminal binding site yielded iron chelates with similar efficacy for hydroxyl radical catalysis. Pseudomonas elastase and HOCl treatment also decreased the ability of apotransferrin to inhibit hydroxyl radical formation by a Fe-NTA supplemented hypoxanthine/xanthine oxidase system. However, apotransferrin could be protected from the effects of HOCl if bicarbonate anion was present during the incubation. Apolactoferrin inhibition of hydroxyl radical generation was unaffected by any of the four proteases or HOCl. Alteration of transferrin by enzymes and oxidants present at sites of pseudomonas and other bacterial infections may increase the potential for local hydroxyl radical generation thereby contributing to tissue injury.
...
PMID:Pseudomonas and neutrophil products modify transferrin and lactoferrin to create conditions that favor hydroxyl radical formation. 165 25

Although some degree of structural homology has been demonstrated among lactoferrins of different species, other reports suggest that these proteins are immunologically distinct. Human, bovine, and porcine lactoferrins were purified to homogeneity from colostral whey by affinity chromatography on immobilized single-stranded DNA. Evidence for shared antigenic determinants among human, bovine, and porcine lactoferrins was demonstrated by Ouchterlony immunodiffusion and immuno "dot" blots using whole antisera and purified Ig directed against each species of lactoferrin. There was no evidence that human transferrin was recognized by any of the lactoferrin-specific antisera evaluated. The degree of cross-reactivity between the lactoferrins and their trypsin digestion products was also evaluated after SDS-PAGE by immunoblotting. These data demonstrate that human, porcine, and bovine lactoferrins share common antigenic determinants and are likely to be more homologous in tertiary structures than suggested previously. Thus, investigations of human or bovine lactoferrin metabolism in infants that are based upon immunologic methods alone should be conducted cautiously in those cases where the presence of both human and bovine lactoferrin is suspected.
...
PMID:Structural homology of human, bovine, and porcine milk lactoferrins: evidence for shared antigenic determinants. 169 71

Metal-binding proteins (ceruloplasmin, transferrin, ferritin, and lactoferrin), proteinase inhibitors (alpha 1-antitrypsin, alpha 2-macroglobulin and inter-alpha-trypsin inhibitors), and albumin were assayed in synovial fluid obtained from 20 patients with rheumatoid arthritis (RA) and 15 with osteoarthritis (OA). The levels of proteinase inhibitors and metal-binding proteins, except transferrin, were significantly increased in synovial fluid from RA patients as compared with synovial fluid from OA patients. Metal-binding proteins significantly correlated with rheumatoid factor and immune complexes in synovial fluid from RA patients. Proteinase inhibitor levels also significantly correlated with C-reactive protein, and complement components. These results suggest that the raised level of metal-binding proteins and proteinase inhibitors in synovial fluid from RA patients reflect inflammatory activity, and hence may play an important role in the pathogenesis of inflammatory joint diseases.
...
PMID:Correlation of metal-binding proteins and proteinase inhibitors with immunological parameters in rheumatoid synovial fluids. 170 87

The antibacterial properties of enzymatic hydrolysates of bovine lactoferrin were examined to determine whether active peptides are produced from this protein. Hydrolysates prepared by cleavage of lactoferrin with porcine pepsin, cod pepsin, or acid protease from Penicillium duponti showed strong activity against Escherichia coli O111, whereas hydrolysates produced by trypsin, papain, or other neutral proteases were much less active. Low molecular weight peptides generated by porcine pepsin cleavage of lactoferrin showed broad-spectrum antibacterial activity, inhibiting the growth of a number of Gram-negative and Gram-positive species, including strains that were resistant to native lactoferrin. The antibacterial potency of the hydrolysate was at least eightfold greater than that of undigested lactoferrin with all strains tested. The active peptides retained their activity in the presence of added iron, unlike native lactoferrin. The effect of the hydrolysate was bactericidal as indicated by a rapid loss of viability of E. coli O111. The lactoferrin hydrolysate described in the present study has commercial value as a natural preservative agent for use in foods and cosmetics, and as a functional component of new clinical foods for prevention or treatment of gastrointestinal disease.
...
PMID:Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin. 178 85

Two forms of lactoferrin, an intact lactoferrin and a "nicked" but apparently intact (i.e., 78-kDa) form, have been isolated from the urine of preterm infants fed human milk. These two forms of lactoferrin, demonstrated to be entirely of maternal origin, were copurified using affinity columns of immobilized single-stranded DNA-agarose. The relative concentrations of the intact lactoferrin and the "nicked" lactoferrin were determined after denaturation and separation by reverse-phase HPLC. N-terminal sequence analyses showed that the intact 78-kDa form had lost two residues from its N terminus. The nicked 78-kDa form was composed of only two fragments; one fragment was identified as the N terminus of the N-lobe (residues 3-283). The other fragment started with Ser-284 and included the alpha-helical structures at the C terminus of the N-lobe, as well as the entire C-lobe. Although no disulfide bonds connect these two fragments, they were tightly associated in vivo and were not separated in vitro except under denaturing conditions. Limited in vitro digestion of human milk lactoferrin with trypsin produced a nicked, but stable (78-kDa), form of DNA-binding lactoferrin nearly indistinguishable from the isolated urinary lactoferrin, except for the absence of one additional arginine residue at the N terminus of the N-lobe. Residues involved in the stable molecular interaction between fragments were evaluated using data obtained from the high-resolution crystal structure of hololactoferrin. Two features, entirely within the N-lobe, account for the lack of fragment dissociation after cleavage at residue 283 in vivo: an extensive interface at the hinge region behind the iron-binding cleft and an "anchor" sequence traversing the remainder of the N-lobe at 90 degrees relative to the fragment interface. These results document the remarkably limited degradation of absorbed lactoferrin in vivo and suggest that iron-binding activity, receptor-binding properties, and postulated immune cell regulatory functions remain intact.
...
PMID:Structurally intact (78-kDa) forms of maternal lactoferrin purified from urine of preterm infants fed human milk: identification of a trypsin-like proteolytic cleavage event in vivo that does not result in fragment dissociation. 201 20


1 2 3 4 5 6 7 8 9 10 Next >>

---