Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The involvement of adenosine in the coupling of insulin binding to action was investigated in rat adipocytes. Reduction of endogenous adenosine levels by treatment with adenosine deaminase (ADA) had no significant effect on either basal or maximally stimulated glucose transport, but reduced the insulin sensitivity of transport stimulation. Adenosine deaminase treatment also shifted the EC50 of H2O2 stimulation of transport from 0.13 mM to 0.30 mM, and the EC50 for insulin stimulation of protein synthesis from 0.40 +/- 0.06 ng/ml to 1.30 +/- 0.25 ng/ml. Adenosine appears to be acting through the pharmacological Ri adenosine receptor subtype. The mode of action of adenosine does not seem to involve inhibition of adenylate cyclase. Adenosine also influences the kinetics of insulin action. ADA treatment slows the onset of transport stimulation by a maximal insulin concentration (10 ng/ml). Increasing the hormone level to 100 ng/ml overcomes this slowing without increasing transport further. The deactivation of glucose transport following removal of insulin is accelerated by ADA treatment. Thus, adenosine is involved both in maintaining a high efficiency of an early step in the insulin signaling process and in maintaining optimal activity of the insulin-stimulated glucose transport system.
Mol Cell Endocrinol 1988 Nov
PMID:The role of adenosine in insulin action coupling in rat adipocytes. 285 Sep 47

In this study we prepared sarcolemmal fractions from bovine and rat hearts; their Na+K+ ATPase activities, measured in the presence of saponin to unmask latent Na+K+ ATPase, were 59.4 and 48.8 mu mol Pi/mg protein.h, respectively. The rate of Na+ dependent Ca2+ uptake was linear for the first 10 s and a plateau was reached in 3 min. Oxidation by free radical generation either with H2O2, FeSO4 plus DTT or xanthine oxidase plus hypoxanthine stimulated Na+/Ca2+ exchange in a time-dependent manner. The stimulation was abolished by deferoxamine or o-phenanthroline. By contrast, oxidation by HOCl inhibited Na+/Ca2+ exchange in proportion to its concentration, and this inhibition was antagonized by DTT. DTT alone had no effect on the exchange. Insulin stimulated Na+/Ca2+ exchange, its maximal effect was attained after 30 min incubation with 100 mu units/ml. N-ethylmaleimide inhibited the exchange both in the presence and in the absence of insulin. Sarcolemmal fractions prepared from hearts of alloxan-treated, acutely diabetic rats showed a significant decrease in Na+/Ca2+ exchange. Addition of insulin in vitro significantly stimulated Na+/Ca2+ exchange of both diabetic and control groups. The results indicate that sarcolemmal Na+/Ca2+ exchange function is modulated by oxidation-reduction states and by the presence of insulin.
Mol Cell Biochem 1988 Sep
PMID:Na+/Ca2+ exchange of isolated sarcolemmal membrane: effects of insulin, oxidants and insulin deficiency. 285 14

The ability of the polymorphonuclear leukocyte (PMN) oxidants, hypochlorous acid (HOC1) and hydrogen peroxide (H2O2), to oxidize proteins in rat heart and lung tissues was investigated. Cardiac myocytes, heart tissue slices, isolated perfused hearts, and lung tissue slices, were treated with HOC1 and H2O2 and the extent of methionine and cysteine oxidation was determined in the cellular proteins. Cardiac tissues were found to be highly susceptible to oxidation by physiological concentrations of HOC1. For example, in isolated hearts perfused for 60 min with 100 microM HOC1, approximately 18% of the methionine and 28% of the cysteine residues were oxidized. Lung tissues, unlike those of the heart, were resistant to physiological concentrations of HOC1, showing no oxidation of proteins. HOC1 was much more effective than H2O2 in oxidizing proteins, suggesting that HOC1 may be the most reactive oxidant produced by activated PMN. These studies show that PMN oxidants, in particular HOC1, can cause significant oxidation of proteins in target tissues, and may therefore constitute a primary cause of tissue injury at sites of inflammation. In addition, these studies show that different tissues may have varying susceptibilities to PMN oxidants.
Mol Cell Biochem 1988 Dec
PMID:Oxidation of proteins in rat heart and lungs by polymorphonuclear leukocyte oxidants. 285 71

The direct effect of oxygen metabolites was studied on isolated perfused rat hearts. Superoxide anion (O2-.) and hydrogen peroxide (H2O2) were generated by adding purine (2.3 mM) and purified xanthine oxidase (0.06 U/ml) to Krebs-Henseleit buffer (pH 7.4). Xanthine oxidase was added to the purine-containing perfusate either near the aorta (group A, which gave H2O2 less than 10 microM) or at a distant point from the aorta (group B, which gave 250 to 300 microM H2O2). The generation rate of O2-. was 31.7 +/- 1.0 nmol/ml/min in the experimental conditions. Contractile function, tissue adenosine triphosphate (ATP), and ultrastructure were not affected in group A. In contrast, hearts in group B showed marked decrease in contractility (+dP/dt) to 24.4 +/- 4.3% of control values. ATP levels were also markedly reduced from control values of 23.4 +/- 0.7 to 7.4 +/- 0.7 mumol/g dry tissue. Ultrastructure in group B hearts revealed "wavy" and disintegrated sarcolemma, depletion of glycogen deposits, and swelling and disruption of mitochondria. Release of the thiobarbituric acid reactive products including malondialdehyde was significant in the effluent (1.68 +/- 0.17 nmol/min/g wet tissue). These changes were almost completely prevented by catalase, but not by superoxide dismutase and deferoxamine. Moreover, exogenous H2O2 perfusion (300 microM) showed results similar to group B hearts. These observations suggest that H2O2 plays a major role in the injury. O2- does not appear to damage hearts directly, although it is important as a precursor of H2O2 and other radical species including hydroxyl radical.
J Mol Cell Cardiol 1988 Nov
PMID:Myocardial dysfunction and ultrastructural alterations mediated by oxygen metabolites. 285 30

Doxorubicin (Adriamycin) and daunomycin analogs have been examined for their ability to chelate iron and catalyze the oxidative cleavage of DNA. The results show that the C-11-hydroxyl group is essential for iron binding and DNA damage. Thus, the iron complexes of doxorubicin, daunomycin, carminomycin, and 4-demethoxydaunomycin are potent redox catalysts capable of reducing molecular oxygen in the presence of physiologic concentrations of glutathione. They are also effective catalysts of hydroxyl radical formation from hydrogen peroxide. With the exception of daunomycin, generation of hydroxyl radical from hydrogen peroxide is stimulated by greater than 200% by DNA addition. Analogs that lack the C-11-hydroxyl group are relatively inefficient at oxygen reduction, hydroxyl radical formation, and DNA cleavage. The potencies of the anthracycline analogs tested in the H2O2-dependent DNA cleavage reaction correlated well with their relative cardiac toxicities.
Mol Pharmacol 1985 Mar
PMID:Thiol-dependent DNA damage produced by anthracycline-iron complexes. The structure-activity relationships and molecular mechanisms. 298 84

The relationship between the generation of active species of oxygen (O-2, H2O2 and OH.), chemiluminescence, and the release of lysosomal enzymes (lysozyme, alpha-mannosidase and beta-glucuronidase) was examined in human neutrophils stimulated with opsonized zymosan in the presence or absence of active-oxygen scavengers. In the absence of scavengers, increasing zymosan concn stimulated a marked increase in active-oxygen production in a concn-dependent manner and a less rigorously dose-dependent increase in enzyme secretion. Addition of OH. and/or 1O2 scavengers (benzoate, 1,4-diazo-bicyclo-2,2,2-octane or xanthine) caused a marked increase in enzyme release and a decrease in the generation of active-oxygen species except O-2 and H2O2. These findings suggest that exocytosis of lysosomal enzymes by stimulated neutrophils might be attenuated by the active generation of OH. and chemiluminescence. Superoxide dismutase (SOD) at low concns inhibited lysosomal enzyme release while promoting OH formation; and SOD at high concns decreased OH. and O-2 formation and chemiluminescence, accompanied by higher levels of lysosomal enzyme release. Catalase showed an effect similar to that of SOD. Our data suggest that the reduction by scavengers of active-oxygen levels, particularly of the species detected in the OH. and chemiluminescence assays, results in an increase in lysosomal enzyme release.
Mol Immunol 1985 Aug
PMID:Reverse relationship between lysosomal-enzyme release and active-oxygen generation in stimulated human neutrophils. 299 96

Thyroglobulin iodination and thyroxine synthesis in vitro require the presence of peroxidase, H2O2 and iodide. H2O2 is usually continuously generated by glucose oxidase (GO) and glucose. The aim of this study was to investigate whether the two enzymes could possibly be inactivated by a particular concentration of H2O2 or iodide present during incubation. The results revealed that both enzymes were indeed inactivated under two distinct conditions: Lactoperoxidase and thyroid peroxidase were inactivated by modest concentrations of H2O2 accumulating during incubation. Glucose oxidase was inactivated by an oxidized species of iodine or singlet oxygen produced in the catalytic cycle. The results may explain some hitherto unsolved discrepancies between different iodination procedures. Moreover they may have an impact on the regulation of in vivo thyroglobulin iodination and hormone synthesis.
Mol Cell Endocrinol 1986 Jul
PMID:Inactivation of peroxidase and glucose oxidase by H2O2 and iodide during in vitro thyroglobulin iodination. 301 6

Patients whose cells are deficient in the glycoproteins LFA-1, Mol, and p150,95 have recurrent infections and pronounced abnormalities in neutrophil adherence, aggregation, chemotaxis, and phagocytosis. We characterized activation and regulation of oxidative metabolism of Mol-deficient neutrophils. These cells failed to depolarize or to produce O2- or H2O2 normally when stimulated by opsonized zymosan. The chemotactic peptide formyl methionyl-leucyl-phenylalanine depolarized Mol-deficient neutrophils normally but caused supernormal production of O2- and H2O2, a result of a prolonged burst in oxidative metabolism. Phorbol myristate acetate depolarized Mol-deficient neutrophils at a nearly normal rate but evoked release of significantly less O2- and H2O2 than from normal PMN. The aberrant activation and regulation of the oxidative burst in Mol-deficient neutrophils are considered in light of recently emerging concepts in the cell biology of this process, and the possibility that these abnormalities reflect a defect in the cytoskeleton-membrane interaction is discussed.
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PMID:Aberrant activation and regulation of the oxidative burst in neutrophils with Mol glycoprotein deficiency. 301 97

The thiol moiety is prone to oxidative free radical formation, which may be important in mediating the toxicity of some thiol-containing compounds. The oxidation of the compounds cysteine, cysteamine, N-acetylcysteine, glutathione, penicillamine, and captopril were studied using ESR and oxygen uptake techniques. Lactoperoxidase, with hydrogen peroxide to provide oxidizing equivalents, was used to initiate the oxidation. The reaction appears to be strongly peroxide dependent, with either exogenous H2O2 or thiol-derived peroxide driving the reaction.
Mol Pharmacol 1987 Apr
PMID:Oxidation of thiol drugs and biochemicals by the lactoperoxidase/hydrogen peroxide system. 303 67

It is well known that the partial reduction of oxygen can result in the formation of highly reactive oxygen products. Hydrogen peroxide is one of these metabolites of oxygen. Peroxidases utilize this metabolite for a variety of functions. It is the purpose of this treatise to review the nature and function of various membrane peroxidases in the body.
Mol Cell Biochem 1988 Oct
PMID:Membrane peroxidases. 305 72


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