Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The appearance of the adult respiratory distress syndrome (ARDS) during the course of acute illness is believed to result, in part, from intrapulmonary neutrophil sequestration and degranulation induced by circulating inflammatory mediators. To evaluate the role of complement-neutrophil interactions in the pathogenesis of ARDS in man, 34 patients suffering from intra-abdominal sepsis (seven), multisystem trauma (15), or acute pancreatitis (12) were serially studied with regard to neutrophil migratory responses to C5a and F-Met-Leu-Phe, lysosomal content of beta-glucuronidase and lysozyme, and simultaneously obtained plasma levels of immunoreactive C3adesArg and C5adesArg. Nineteen patients developed ARDS. In these patients, plasma C3adesArg levels obtained within 72 hours of admission to the hospital were elevated to 305 +/- 35 ng/ml compared with 145 +/- 16 ng/ml for patients who did not develop ARDS (p less than 0.0005). C5adesArg levels were not elevated in either group. In vitro studies showed that neutrophils from normal persons were able to clear all of the C5a/C5adesArg generated in up to 5% zymosan-activated serum, while no clearance of C3adesArg was identified. Patient migratory responses could be divided into three groups based on their initial (less than 72 hour) samples: (1) hyperresponsive to both N = formyl-methionyl-leucyl-phenylalanine (FMLP) and C5a, (2) specifically deactivated to C5a, and (3) deactivated to both C5a and FMLP. Patients in the latter two groups developed ARDS. Enzyme content of neutrophils from patients who developed ARDS showed a substantial fall in beta-glucuronidase and lysozyme levels. The finding of elevated plasma C3a levels and deactivation of migratory response to C5a support the contention that complement activation had occurred in these patients and that their neutrophils had been exposed to C5a/C5adesArg in vivo. The finding of nonspecific migratory dysfunction associated with lysozymal enzyme loss, a circumstance not reproducible in vitro by C5a exposure, suggests that other stimuli produced degranulation of neutrophils made hyperresponsive by prior exposure to C5a.
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PMID:Complement activation and clearance in acute illness and injury: evidence for C5a as a cell-directed mediator of the adult respiratory distress syndrome in man. 400 15

By application of pulse radiolysis it was demonstrated that nitrogen dioxide (NO2.) oxidizes Gly-Tyr in aqueous solution with a strongly pH-dependent rate constant (k6 = 3.2 X 10(5) M-1 S-1 at pH 7.5 and k6 = 2.0 X 10(7) M-1 S-1 at pH 11.3), primarily generating phenoxyl radicals. The phenoxyl can react further with NO2. (k7 approximately 3 X 10(9) M-1 S-1) to form nitrotyrosine, which is the predominant final product in neutral solution and at low tyrosyl concentrations under gamma-radiolysis conditions. Tyrosine nitration is less efficient in acidic solution, due to the natural disproportionation of NO2., and in alkaline solutions and at high tyrosyl concentrations due to enhanced tyrosyl dimerization. Selective tyrosine nitration by interaction of NO2. with proteins (at pH 7 to 9) was demonstrated in the case of histone, lysozyme, ribonuclease A, and subtilisin Carlsberg. Nitrotyrosine developed slowly also under incubation of Gly-Tyr with nitrite at pH 4 to 5, where NO2. is formed by acid decomposition of HONO. It is recalled in this context that NO2.-induced oxidations, by regenerating NO2-, can propagate NO2./NO2- redox cycling under acidic conditions. Even faster than with tyrosine is the NO2.-induced oxidation of cysteine-thiolate (k9 = 2.4 X 10(8) M-1 S-1 at pH 9.2), involving the transient formation of cystinyl radical anions. The interaction of NO2. with Gly-Trp was comparably slow (k approximately 10(6) M-1 S-1), and no reaction was detectable by pulse radiolysis with Met-Gly and (Cys-Gly)2, or with DNA. Slow reactions of NO2. were observed with arachidonic acid (k approximately 10(6) M-1 S-1 at pH 9.0) and with linoleate (k approximately 2 X 10(5) M-1 S-1 at pH 9.4), indicating that NO2. is capable of initiating lipid peroxidation even in an aqueous environment. NO2.-Induced tyrosine nitration, using 50 microM Gly-Tyr at pH 8.2, was hardly inhibited, however, in the presence of 1 mM linoleate, and was not affected at all in the presence of 5 mM dimethylamine (a nitrosamine precursor). It is concluded that protein modifications, and particularly phenol and thiol oxidation, may be an important mechanism, as well as initiation of lipid peroxidation, of action of NO2. in biological systems.
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PMID:Reactions of nitrogen dioxide in aqueous model systems: oxidation of tyrosine units in peptides and proteins. 406 99

The effects of the co-carcinogenic phorbol ester, phorbol myristate acetate (PMA), on N-formyl-Met-Leu-Phe (FMLP)-induced human polymorphonuclear leukocyte chemokinesis and release of granular lysozyme and beta-glucuronidase were compared with those of the inactive phorbol didecanoate (PDD). Release of the enzymes was enhanced by PMA but was unaffected by PDD which also had no effect on chemokinesis. In contrast, FMLP-induced chemokinesis was completely suppressed by PMA in a dose-dependent fashion (ID50 = 3.5 nM). PMA also inhibited the FMLP-induced increase in cytoplasmic calcium level, measured by the fluorescent indicator quin-2. These and other results suggest that although the diacylglycerol/protein kinase C system is involved in the positive regulation of certain neutrophil functions (degranulation and superoxide generation), if it is very powerfully stimulated, as with PMA, it has inhibitory actions on other neutrophil properties such as motility.
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PMID:Phorbol myristate acetate enhances human polymorphonuclear neutrophil release of granular enzymes but inhibits chemokinesis. 406 81

The effect of modification of maleimide derivatives on superoxide production by guinea-pig neutrophils induced by a variety of different soluble stimuli was studied. Pretreatment of neutrophils by showdomycin, a very slowly penetrating-SH reagent, did not affect superoxide production by all of the stimuli used, suggesting no exposure of sulfhydryl groups involved in superoxide-generating system on the cell surface. Pretreatment with N-ethylmaleimide (MalNEt), a considerably penetrating-SH reagent, markedly inhibited superoxide production stimulated by formyl-methionyl-leucyl-phenylalanine (HCO-Met-Leu-Phe), cytochalasin E or digitonin, but not superoxide production stimulated by the ionophore A23187 or sodium fluoride. The oxygen consumption stimulated by HCO-Met-Leu-Phe or cytochalasin E was inhibited by MalNEt pretreatment, whereas the oxygen consumption stimulated by A23187 was not inhibited by MalNEt. The inhibition by MalNEt of superoxide production did not appear to be due to the interference with binding of the affected stimuli, since MalNEt pretreatment did not inhibit the release of lysozyme, granule enzyme, induced by HCO-Met-Leu-Phe, cytochalasin E or digitonin. Particulate fractions from MalNEt-pretreated neutrophils before exposure to the stimulus exhibited the inhibition of the enhancement of NADPH-dependent superoxide production induced by HCO-Met-Leu-Phe, cytochalasin E or digitonin, but not A23187, whereas treatment of neutrophils with MalNEt after activation by these stimuli had no effect on the NADPH oxidase activity in particulate fractions. Direct exposure of particulate fractions from A23187-stimulated neutrophils to MalNEt showed no actual susceptibility of NADPH oxidase to MalNEt inhibition. These findings suggest that the inhibitory effect of MalNEt is caused by the modification of the process of the activation by the affected stimuli of the superoxide system, probably NADPH oxidase and that at least two mechanisms exist for activation of superoxide-generating system in guinea-pig neutrophils on the basis of the susceptibility to MalNEt inhibition.
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PMID:Effect of maleimide derivatives on superoxide-generating system of guinea-pig neutrophils stimulated by different soluble stimuli. 609 85

Pretreatment of rabbit peritoneal neutrophils at 37 degrees with 10-35 microM L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK) decreases by 20-50% the detectable number of f Met-Leu-[3H]Phe binding sites. Greater TPCK concentrations, between 50 and 100 microM, cause less of a decrease or actually increase peptide binding activity to a level greater than that of untreated cells. Furthermore, Scatchard analysis indicates that the sites detected on neutrophils after TPCK treatment have 1.2-3.2 fold lower apparent Kd (higher affinity) than those detected on untreated, control cells (1.1 +/- 1.7 X 10(-8) M vs 1.7 +/- 1.5 X 10(-8) M, P less than 0.02). Thus, TPCK treatment of rabbit peritoneal neutrophils causes both a decrease in f Met-Leu-[3H]Phe receptors and increases the affinity of the remaining sites. In addition, peritoneal neutrophils incubated at 37 degrees without TPCK were found to rapidly express additional f Met-Leu-[3H]Phe receptors. These additional sites, however, were not evident on neutrophils incubated at 37 degrees with TPCK. Concomitantly with the expression of additional sites, neutrophils placed at 37 degrees were found to spontaneously release small amounts of lysozyme. However, since equivalent amounts of lysozyme were released by cells incubated with or without TPCK, we are unable to state whether expression of the additional sites is due to neutrophil degranulation. Finally, although rabbit peripheral blood neutrophils also show an increase in binding sites at 37 degrees, treatment of these cells with TPCK does not cause a decrease in their f Met-Leu-[3H]Phe binding activity.
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PMID:The formylpeptide chemotactic receptor on rabbit peritoneal neutrophils: change of receptor affinity and number by L-1-tosylamide-2-phenylethyl chloromethyl ketone (TPCK). 631 80

We report a study of the relative reactivity of the common amino acids and of their residues in lysozyme with osmium tetroxide, the osmium tetroxide-pyridine reagent, and with the oxo-osmium(VI)-pyridine reagent. With free amino acids, the osmium(VIII) reagents are most reactive with Met, Cys, His, Thr, Ser, Trp, Lys, and Pro; the osmium(VI) reagent only reacts significantly with His, Met, Cys, Thr, and Ser. In lysozyme, only Cys, Met, and Trp react extensively with the osmium(VIII) reagents; with the osmium(VI) reagent, Cys and Met are most reactive. We also note evidence both for cross-linking of proteins and for peptide bond cleavage, which appears to have considerable specificity for tryptophanyl residues.
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PMID:Reaction of osmium reagents with amino acids and proteins. Reactivity of amino acid residues and peptide bond cleavage. 730 53

The synthesis and the biological activity towards human neutrophils of some N-formyl-Met-Leu-Phe-OMe analogues containing (S)-phenylalaninol (Pheol) or its derivatives in place of the native phenylalanine are reported. While the analogue containing Pheol (4) was found to be devoid of significant biological activity, its esters 3 and 5, although inactive as chemoattractants, are able to strongly stimulate superoxide production and are active with a lower efficacy in the lysozyme release.
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PMID:Chemotactic peptide analogues. Synthesis and chemotactic activity of N-formyl-Met-Leu-Phe analogues containing (S)-phenylalaninol derivatives. 748 25

A gamma-glutamyl peptide-hydrolysing enzyme was partially purified from Actinobacillus actinomycetemcomitans. The enzyme required metal ions, and 1 to 2 mM Mn2+ ions, especially, were essential for hydrolytic reaction. Its distribution by treatment of cells with lysozyme-EDTA suggested that the enzyme was a membrane-bound protein. The pI of the enzyme was in range of pH 5.1 to 5.6, and the apparent Km value for gamma-glutamyl-p-nitroanilide was 3.0 x 10(-4) M. The enzyme hydrolysed specifically gamma-glutamyl residues from the N-terminal of gamma-glutamyl compounds such as gamma-Glu-Met, gamma-Glu-Ala, gamma-Glu-Leu and gamma-Glu-Tyr, but did not catalyse the transpeptidation reaction. Neither free amino acids such as Ala-, Pro-, Gly- and Leu-p-nitroanilide nor alpha-glutamyl derivatives were hydrolysed. Its activity was strongly inactivated by metal chelators (EDTA or o-phenanthroline) and amino acids (Glu, Gln). In addition, the activity was specifically inactivated by gamma-glutamyl affinity-labelling reagents such as AT-125, 6-diazo-5-oxo-L-norleucine and azaserine, which are inhibitors of the gamma-glutamyl donor sites of mammalian gamma-glutamyl transpeptidase. Antibodies against bovine kidney gamma-glutamyl transpeptidase decreased the activity of the bacterial enzyme by 65%. These results suggested that the active sites in the bacterial enzyme were similar to those in mammalian gamma-glutamyl transpeptidase.
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PMID:Partial purification and some properties of gamma-glutamyl peptide-hydrolysing enzyme from Actinobacillus actinomycetemcomitans. 779 32

For-Met-delta ZLeu-delta ZPhe-OMe (3) has been synthesized as a new analogue of the prototypical chemotactic agent For-Met-Leu-Phe-OMe (fMLP-OMe). Compound 3 is characterized by presence of two consecutive alpha,beta-didehydro amino acid residues [delta ZLeu = (Z)-alpha,beta-didehydroleucine; delta ZPhe = (Z)-alpha,beta- didehydrophenylalanine] located at the central and C-terminal position, respectively. When tested on human neutrophils the N-formyltripeptide 3, although less active than the parent, is able to induce chemotaxis, superoxide anion production and lysozyme release. The activity of 3 has been compared to that of related fMLP-OMe analogues containing a single delta ZPhe residue located at the C-terminal position.
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PMID:Modified chemotactic peptides: synthesis and biological activity of HCO-Met-delta ZLeu-delta ZPhe-OMe. 783 75

For-Thp-Leu-delta ZPhe-OMe (2), an analogue of the chemotactic tripeptide For-Met-Leu-Phe-OMe, containing 4-aminotetrahydrothiopyran-4-carboxylic acid (Thp) and (Z)-2,3-didehydrophenylalanine (delta ZPhe) as achiral, conformationally restricted mimics of Met and Phe, respectively, has been synthesized. In the crystal the new formyltripeptide adopts a type I beta-turn conformation stabilized by a weak H bond between the formylic oxygen and the delta ZPhe NH. 1H-nmr analysis based on NH solvent accessibility and nuclear Overhauser effect experiments suggests that the beta-turn is not preferred in CDCl3 solution where a gamma-turn, centered at the Thp residue, prevails. The biological activity of 2 has been determined on human neutrophils and compared to that of previously studied analogues. The tripeptide 2 is practically unable to elicit superoxide anion production and lysozyme release, while slight, but not statistically significant activity was induced in chemotaxis. The role of the orientation of the aromatic ring with respect to the backbone adjacent atoms is discussed.
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PMID:Modified chemotactic peptides: synthesis, conformation, and biological activity of For-Thp-Leu-delta ZPhe-OMe. 794 17


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