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)

Human peripheral blood monocytes, isolated in high purity by centrifugal counterflow elutriation from normal donors, release cell toxins, herein termed human monocyte toxins (HMTs) upon further stimulation in vitro. The principal form of HMTs produced by these human peripheral blood monocytes has been subjected to biochemical, functional, and serological characterization. By molecular sieving on Sephacryl S-200, HMTs can be resolved into two molecular weight classes. The larger, termed alpha, has a molecular weight of about 120,000, and the smaller, termed beta, has a molecular weight of about 65,000. The beta class is by far the most predominant species and has been further characterized. Chromatofocusing of beta-HMT indicates a slightly acidic nature, since this species is eluted at pH 5.8. Functional characterization of beta-HMT suggests that it is not a trypsin-like protease, since neither alpha,N-tosyl-L-lysylchloromethylketone nor alpha,N-tosyl-L-arginyl methyl ester are capable of causing significant inhibition of the cell-lytic activity of the molecule. Furthermore, cell lysis induced by beta-HMT appears to be independent of oxygen-dependent mechanisms, since catalase is incapable of blocking lysis, and since hydrogen peroxide and superoxide anion are not produced in detectable amounts during lysis. Finally, beta-HMT does not appear to be an arginase, since it is active in arginine-containing medium and further addition of arginine to the assay medium does not inhibit lysis significantly. beta-HMT is serologically related to recombinant human tumor necrosis factor (rHuTNF), since its cell lytic activity can be blocked by a rabbit antiserum against rHuTNF. However, much higher levels of this antiserum are required to achieve neutralization than are required to neutralize a comparable number of cell lytic units of rHuTNF. Furthermore, the results of preliminary immunoprecipitation experiments using the rabbit anti-rHuTNF antiserum suggest that a peptide in the Mr 60,000-70,000 range is recognized by this serum, whereas no signal at Mr 17,000 corresponding to rHuTNF is detectable. Thus, human peripheral blood monocytes can be triggered to release cell toxins, the principal form of which, beta-HMT, appears to be functionally distinct from the cytotoxic proteases reported in the murine system and appears to be molecularly distinct from, but serologically related to rHuTNF.
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PMID:Effector mechanisms of human monocyte-mediated tumor cytotoxicity in vitro: biochemical, functional, and serological characterization of cytotoxins produced by peripheral blood monocytes isolated by counterflow elutriation. 369 12

Additions of micromolar concentrations of hematin to washed rat pulmonary microsomal preparations resulted in marked (5-7-fold) increases in the NADPH-dependent generation of phenolic metabolites of benzo[a]pyrene (BaP). 9-Hydroxy-BaP was identified as the major reaction product. Additions of pulmonary cytosolic fractions to microsomes produced no measurable effect but cytosol and hematin added together elicited 25-30-fold increases in total phenolic products. Cytosolic fractions from other tissues, including rat kidneys and perfused rat livers, were also highly effective in enhancing the hematin-mediated increases in monooxygenase activity. However, cytosol from human placental tissues was only minimally effective when either pulmonary or placental microsomes were utilized as enzyme source. Superoxide dismutase and catalase (alone or in combination) had no measurable effect on hematin-mediated increases. Horseradish peroxidase effectively inhibited the hematin-dependent reactions but hematin-independent reactions were inhibited with equal effectiveness. Carbon monoxide profoundly inhibited all hematin-mediated increases in metabolite formation. The activating cytosolic component was non-dialyzable, inactivated by trypsin and heat, and eluted in the void volume from Sephadex G-150 columns. This suggested that the cytosolic factor(s) responsible for the increased hematin-dependent oxidation was a protein(s) with a high molecular weight or perhaps an aggregate or oligomer of proteinaceous material. HPLC profiles indicated a major effect on the generation of phenolics; quinones were also increased but only minimal increases in diols were observed. Results were consistent with the hypothesis that hematin-mediated increases in pulmonary monooxygenase activity result from an increased association of a small pool of pulmonary P-450-apoprotein(s) with the hematin prosthetic group to result in increased levels of an unidentified holocytochrome(s) with a relatively high substrate turnover number. The current data suggest a quaternary interaction among P-450 apoprotein(s), heme prosthetic group, reaction products (particularly 3-hydroxy-BaP) and a cytosolic protein(s). We postulate that the mechanism of action of the cytosolic factor is to facilitate the interaction of hematin with the apocytochrome.
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PMID:Cytosolic activation of hematin-dependent microsomal monooxygenase activity in the lung. 370 23

Benzoyl- and isopentenoyl phosphoric triamides (BPA and IPA) strongly inhibited urease activities from jack bean, soybean, watermelon seed, Proteus mirabilis, P. rettgeri, P. vulgaris, Mycobacterium smegmatis, and Ureaplasma urealyticum. Their I50 values (the final concentration causing 50% inhibition), independent of enzyme source, were 2-21 nM, which are about 1,000-fold lower than that of caprylohydroxamic acid, one of the most potent urease inhibitors. ATP-urea amidolyase activity was inhibited 50% by BPA at a higher concentration of 0.28 mM, but was not affected by IPA even at 1.3 mM. Thirteen kinds of hydrolases (trypsin, chymotrypsin, thermolysin, leucine aminopeptidase, papain, lipase, alpha-amylase, glucuronidase, asparaginase, arylsulfatase, alkaline phosphatase, acid phosphatase, and true cholinesterase), two oxidoreductases (catalase and alcohol dehydrogenase), three transferases (glutamic-oxaloacetic aminotransferase, gamma-glutamyl transpeptidase, and arylsulfotransferase) and two kinases (pyruvate kinase and creatine kinase) were not affected at all even at 1 mM BPA and IPA. Exceptionally, pseudo-cholinesterase from human serum was inhibited by BPA and IPA, whose I50 values were 70 nM and 10 muM, respectively, using acetylthiocholine as a substrate. These values increased to 0.55 muM and 54 muM, respectively, when acetylcholine was used as a substrate. These results show that N-acylphosphoric triamides potently and specifically inhibit urease activity at concentrations of nM order.
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PMID:Specific inhibition of urease by N-acylphosphoric triamides. 384 42

A strain of Streptococcus faecalis isolated from the urogenital flora was selected for its ability to inhibit the in vitro growth of Neisseria gonorrhoeae. Initially, the inhibitory activity was demonstrated on solid medium only when the inhibitor and the target strains were growing simultaneously, such as in the spot-lawn and flip-flop agar overlay methods. The antigonococcal effect was not due to a shift in the pH or depletion of nutrient in the medium. This activity was not produced in liquid medium nor could it be extracted in a soluble form from either the solid medium or the streptococcal cells. The production of the inhibitory activity could not be enhanced by ultraviolet irradiation or treatment with mitomycin C. The composition of the medium was found to affect the size of the inhibitory zone produced. The inhibitory activity showed a wide antigonococcal spectrum and was susceptible to trypsin and pronase but resistant to alpha- and beta-amylases and catalase. This activity passed through a filtering membrane and was also dialyzable and had an apparent molecular weight of less than 1,000. The addition of bovine serum albumin to solid medium enabled us to show an inhibition even when the producer and the target strains were grown sequentially, thus suggesting that part of the difficulty of studying such inhibitory activity could be due to its instability.
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PMID:In vitro inhibition of Neisseria gonorrhoeae growth by a urogenital strain of Streptococcus faecalis. 392 55

Several anticancer drugs were tested for induction of cytolysis mediated by polymorphonuclear leukocytes (PMNs). Among them, actinomycin D and vincristine sulfate induced tumor lysis mediated by PMNs (drug-dependent cellular cytotoxicity). The cell-free supernatant of PMNs incubated with actinomycin D in vitro could lyse various murine tumor cells, although normal spleen cells and sheep red blood cells were not lysed. The cytolytic activity of the supernatant was resistant to treatment with superoxide dismutase, catalase, trypsin inhibitor or arginine. However, the cytolytic activity was labile to heat treatment at 56 degrees (30 min) or trypsin treatment, suggesting a protein nature. These results suggest that PMNs can lyse tumor cells in the presence of certain anticancer drugs and that a factor(s) from PMNs may participate in the killing of tumor cells.
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PMID:Drug-dependent cellular cytotoxicity mediated by polymorphonuclear leukocytes. 392 61

The alpha-oxidation of [1-14C]phytanic acid of high specific activity was studied in postnuclear and various subcellular fractions from rat liver. alpha-Oxidation in the postnuclear fraction required ATP, Mg2+, nicotinamide, and molecular oxygen for activity. alpha-Oxidation was inhibited by iron-specific chelating agents and respiratory chain inhibitors. Partial inhibition by carbon monoxide indicated a possible involvement of cytochrome P-450. However, phenobarbital-treated rat liver postnuclear fraction did not stimulate phytanic acid alpha-oxidation above that of control. Subcellular fractionation indicated that in addition to the mitochondrial fraction, cytosol was required for activity. The cytosolic factor appeared to be dialyzable; it was inactivated by heat treatment, but not affected by trypsin digestion. NAD, CoA, ascorbic acid, and catalase did not replace cytosolic activity nor did the recently characterized heat-stable factors in brain hydroxylation, namely, adenosine nucleotides and glutamate.
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PMID:Phytanic acid alpha-oxidation in rat liver. Requirement of cytosolic factor. 623 33

Since leukocytes comprise a major portion of staphylococcal abscesses, the properties of the bactericidal material in abscess homogenates were compared with those of bactericidal systems associated with leukocyte lysosomes. The bactericidal material in abscess homogenates was distinguished from the myeloperoxidase system by its resistance to heat (100 degrees C, 30 min), lack of solubility in dilute acid (0.005 N HCl), resistance to strong acid (pH 1), and insensitivity to catalase. It was differentiated from the cationic proteins by its lack of solubility in dilute acid, insensitivity to iron (0.1 mM) or trypsin (5 mg/ml), and greater activity in solutions of increased ionic strength. These characteristics, together with its sensitivity to Ca2+ or albumin, suggested that the material might be lipid. Subsequent studies revealed that all the bactericidal activity resided in the lipid fraction recovered after extraction of abscess homogenates by the Dole procedure.
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PMID:Partial characterization of a bactericidal system in staphylococcal abscesses. 625 79

Pretreatment of hemoglobin with 50-5000 nmol hydrogen peroxide (H2O2) increased its susceptibility to proteolysis by a number of purified enzymes, including trypsin, chymotrypsin, elastase, and plasmin, and by the neutral protease of rat peritoneal leukocytes. Pretreatment of the protein substrate with catalase-inactivated H2O2 had no effect. Separation of the proteolytic fragments by G-75 Sephadex gel filtration indicated no apparent differences in the size distribution of the fragments produced by treatment with the H2O2/proteolytic enzyme combination as compared with enzyme treatment alone. A partially purified preparation of rat glomerular basement membrane was also treated with proteolytic enzyme alone or in combination with H2O2. As with the hemoglobin, pretreatment of the glomerular basement membrane with H2O2 increased its susceptibility to subsequent proteolytic attack. In addition, treatment of a basement membrane glycoprotein, fibronectin, with H2O2 also increased its sensitivity to subsequent proteolysis. These results suggest that in addition to their other proinflammatory activities, oxygen-derived metabolites may contribute to tissue destruction by altering the susceptibility of proteins to hydrolytic enzymes.
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PMID:Protein degradation following treatment with hydrogen peroxide. 637 92

The oxygen radical generating system of xanthine oxidase plus xanthine, which has been used as a model for the oxidative burst of activated granulocytes, is known to damage endothelium in vivo and in vitro. We previously observed effects (inhibited by catalase, and thus associated with the formation of H2O2) on several parameters of endothelial function, using a non-commercial preparation of xanthine oxidase. Our present study demonstrates that xanthine oxidase from two different commercial sources has additional effects on endothelial morphology and ion flux that are substrate-independent (i.e. produced in the absence of added xanthine) and are attributable to the presence of pancreatin (a crude enzyme mixture used in the commercial preparation of xanthine oxidase from milk). These effects are related to the tryptic activity of pancreatin and extend previous observations on the effects of neutral proteases on endothelial cells. Our results emphasise the practical point that studies on the effects of commercial xanthine oxidase preparations on endothelial cells must take account of their trypsin-like activity as well as their capacity to generate oxygen products.
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PMID:Stimulation of endothelial cells by protease activity in commercial preparations of xanthine oxidase. 638 77

Seven streptococci isolated from the normal urogenital flora were selected for the production of an inhibitory activity toward Neisseria gonorrhoeae on solid medium. This activity was abolished when catalase was added to the medium in the case of Streptococcus mitis isolates 22, 25, 74 and Streptococcus sanguis II isolate 70 suggesting the involvement of hydrogen peroxide. The inhibitory activities produced by the other isolates (Streptococcus faecalis) were trypsin sensitive (isolates 12 and 14) or stable (isolate 59). Hydrogen peroxide production by S. sanguis II was quantitatively evaluated by reference to a standard curve representing the inhibitory effect of various concentrations of commercial H2O2 on N. gonorrhoeae growth. After 22 h of incubation a yield of 5.3 m mol H2O2 I-1 was reached on solid medium while in liquid medium values of 2.8 and 7.3 m mol H2O2 I-1 were obtained, respectively, in non-agitated and agitated cultures after 8 h of incubation.
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PMID:Inhibition of Neisseria gonorrhoeae growth due to hydrogen peroxide production by urogenital streptococci. 642 55


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