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 effects of surfactant apoprotein A (SP-A) on the superoxide production of rat alveolar macrophages (AM) were studied. Superoxide production was measured by the ferricytochrome c reduction method. When AM were incubated with SP-A only during the measurement of superoxide production, superoxide production was not influenced by SP-A. However, when AM were preincubated with SP-A at a concentration of 1, 2, and 10 micrograms/ml, superoxide production by AM was significantly inhibited (P < 0.05, P < 0.01, P < 0.01, respectively). The superoxide production of AM stimulated by PMA was significantly inhibited by SP-A at a concentration of 1 microgram/ml (P < 0.01), and superoxide production stimulated by zymosan was also inhibited by SP-A at a concentration of 10 micrograms/ml (P < 0.05). Suppression of superoxide production of unstimulated and PMA-stimulated AM was significantly inhibited by anti-SP-A antibody. Superoxide generation by the xanthine and xanthine oxidase system was not affected by the presence of SP-A. Our results suggest that superoxide production of AM can be inhibited by SP-A and that this inhibitory effect on AM is due to a specific effect of SP-A. From these results, it is speculated that SP-A may have a protective role for oxidant injury by AM in the lung.
Am J Respir Cell Mol Biol 1993 Nov
PMID:Rat surfactant apoprotein A (SP-A) exhibits antioxidant effects on alveolar macrophages. 821 93

Studies were carried out to evaluate the ability of human liver microsomes to generate superoxide radical and hydrogen peroxide, and to interact with ferric chelates to produce more potent oxidizing species such as the hydroxyl radical (.OH). In the presence of either NADPH or NADH, human liver microsomes produced superoxide and H2O2 at rates about 20 to 30% of that found with rat liver microsomes. These lower rates are caused, in part, by the 3-fold lower content of total cytochrome P450 in the human liver microsomes. NADH-dependent rates were about 25 to 30% of the NADPH-dependent rates. In the presence of appropriate ferric complexes, human liver microsomes generated .OH, promoted cleavage of vicinal diols, and underwent lipid peroxidation. In contrast to results with rat liver microsomes, NADH-dependent rates of .OH production or lipid peroxidation by human liver microsomes were similar to the NADPH-dependent rates. Human liver microsomes reduced ferric ATP or ferric EDTA at nearly comparable rates with NADPH and NADH. Sensitivity of the various iron-dependent reactions to antioxidants was found to be characteristic of the particular system. These results suggest the possibility that human liver microsomes are an important source of reactive oxygen intermediates, especially under conditions of increased NADH or NADPH availability and elevated iron concentration.
Mol Pharmacol 1994 Jan
PMID:Generation of reactive oxygen intermediates by human liver microsomes in the presence of NADPH or NADH. 830 74

Superoxide dismutase functions as a scavenger of superoxide radical protecting living organisms. This enzyme has potential use as anti-inflammatory or anti-reperfusion injury drug. Here we present a simple and efficient SOD purification method from human placental blood. Superoxide dismutase from clarified haemolysed placental blood after chloroform and ethanol treatment was purified by DEAE-Sepharose, Phenyl-Sepharose chromatographies and cross flow ultrafiltration. The purified product is 98% pure by SDS-PAGE with 71% yield and specific activity of 2.8 x 10(5) U/mg protein.
Biochem Mol Biol Int 1993 May
PMID:Purification of superoxide dismutase from placental haemolisate blood: a simple and efficient method. 835 35

It is well known that antigen challenge of sensitized subjects can induce an immediate and late asthmatic response, airway eosinophilia, and hyperreactivity. Using our modified guinea pig asthma model, we investigated the superoxide anion generation from eosinophils and macrophages recovered from bronchoalveolar lavage (BAL) 24 h after antigen (ovalbumin) challenge. We also investigated the effect of formoterol, a new long-acting selective beta 2-agonist, on these functions. Antigen challenge increased the total cell counts and the ratio of eosinophils in BAL. Eosinophils and macrophages were collected using discontinuous density centrifugation. Antigen challenge enhanced superoxide anion generation from eosinophils, from 5.39 +/- 1.08 to 13.19 +/- 1.95 nmol 60 min after phorbol myristate acetate (PMA) (1 ng/ml) activation, and 0.22 +/- 0.49 to 3.34 +/- 1.67 nmol 40 min after platelet-activating factor (PAF) (10(-6) M) activation. Formoterol treatment before antigen challenge prevented these enhancements. Superoxide anion generation from macrophages was also enhanced by antigen challenge, from 6.57 +/- 0.76 to 10.66 +/- 0.88 nmol 60 min after PMA activation, and 4.20 +/- 1.17 to 6.63 +/- 0.64 nmol 60 min after PAF activation. Formoterol, however, failed to inhibit enhancement of superoxide anion generation from macrophages. These results show antigen challenge of sensitized guinea pigs induces an increase of eosinophils and macrophages in BAL and enhances the functional characteristics of both cells. Formoterol had inhibitory effects on the enhancement of superoxide anion generation from eosinophils but did not have this effect on macrophages.
Am J Respir Cell Mol Biol 1993 May
PMID:Effect of formoterol on superoxide anion generation from bronchoalveolar lavage cells after antigen challenge in guinea pigs. 838 28

Rac1 and Rac2 are closely related, low molecular weight GTP-binding proteins that have both been implicated in regulation of phagocyte NADPH oxidase. This enzyme system is composed of multiple membrane-bound and cytosolic subunits and when activated catalyzes the one-electron reduction of oxygen to superoxide. Superoxide and its highly reactive derivatives are essential for killing microorganisms. Rac proteins undergo posttranslational processing, primarily the addition of an isoprenyl group to a carboxyl-terminal cysteine residue. We directly compared recombinant Rac1 and Rac2 in a human neutrophil cell-free NADPH oxidase system in which cytosol was replaced by purified recombinant cytosolic components (p47-phox and p67-phox). Processed Rac1 and Rac2 were both highly active in this system and supported comparable rates of superoxide production. Under different cell-free conditions, however, in which suboptimal amounts of cytosol were present in the assay mixture, processed Rac2 worked much better than Rac1 at all but the lowest concentrations. This suggests that a factor in the cytosol may suppress the activity of Rac1 but not of Rac2. Unprocessed Rac proteins were only weakly able to support superoxide generation in either system, but preloading of Rac1 or Rac2 with guanosine 5'-O-(3-thio-triphosphate) (GTP gamma S) restored activity. These results indicate that processing is required for nucleotide exchange but not for interaction with oxidase components.
Mol Biol Cell 1993 Mar
PMID:Requirement for posttranslational processing of Rac GTP-binding proteins for activation of human neutrophil NADPH oxidase. 838 55

Superoxide is produced by phagocytic cells at rates sufficient to have cytocidal effects. A wide variety of receptor-dependent and -independent agonists triggers this respiratory burst, including immunoglobin aggregates, complement fragments, and leukotriene B4. Lower rates of O2-. production are triggered by addition of specific cytokines into B-lymphocytes, endothelial cells, fibroblasts, and kidney mesangial cells; low concentration of radicals may act as signals for proliferation or other changes. The NADPH oxidase of phagocytes, characterized by the presence of FAD and a low potential cytochrome b, is organized to transfer electrons electrogenically across the plasma membrane from NADPH to O2. A proton channel permits movement of compensating H+.
Mol Chem Neuropathol
PMID:The mechanism of the production of superoxide by phagocytes. 839 50

Administration of methamphetamine (METH) to animals causes loss of DA terminals in the brain. The manner by which METH causes these changes in neurotoxicity is not known. We have tested the effects of this drug in copper/zinc (CuZn)-superoxide dismutase transgenic (SOD Tg) mice, which express the human CuZnSOD gene. In nontransgenic (non-Tg) mice, acute METH administration causes significant decreases in DA and dihydroxyphenylacetic acid (DOPAC) in the striata of non-Tg mice. In contrast, there were on significant decreases in striatal DA in the METH administration caused decreases in striatal DA and DOPAC in the non-Tg mice, but not in the SOD-Tg mice. Similar studies were carried out with 1-methyl-1,2,3,6-tetrahydropyridine (MPTP), which also causes striatal DA and DOPAC depletion. As in the case of METH, MPTP causes marked depletion of DA and DOPAC in the non-Tg mice, but not in the SOD Tg mice. These results suggest that the mechanisms of toxicity of both METH and MPTP involved superoxide radical formation.
Mol Neurobiol
PMID:Neurotoxicity, drugs and abuse, and the CuZn-superoxide dismutase transgenic mice. 856 59

Electron Spin Resonance and Spin Trapping techniques were used to demonstrate the generation of free radicals during incubation of paraquat with lung microsomes. Aerobic incubation of paraquat resulted in the production of superoxide radical (.O2-) which was trapped by 5, 5-dimethyl-pyrroline-N-oxide or phenyl-tert-butyl-nitrone. The formation of .O2- and hydroxyl radical (.OH) by paraquat during microsomal incubation was also confirmed by the inhibition of the EPR spectra of DMPO-O2- and DMPO-OH spin adducts by superoxide dismutase and dimethyl sulfoxide, respectively. Our results provide direct evidence for the generation of reactive oxygen species during redox cycling of paraquat in microsomes. The formation of DMPO-H spin adduct during incubation of paraquat in the microsomal system is a strong indication of the involvement of hydrogen atom transfer mechanisms in paraquat-induced generations of reactive oxygen species in the lung.
Biochem Mol Biol Int 1995 Oct
PMID:EPR studies of spin-trapped free radicals in paraquat-treated lung microsomes. 867 8

The specificity of 2,2,6,6-tetramethylpiperidine to singlet oxygen was shown using Rose Bengal as a singlet oxygen generator, and Xanthine-Xanthine Oxidase and KO2 as the sources for the superoxide radical. The highest concentration of produced-singlet oxygen occurred at 25% of O2 by Rose Bengal photosensitization. The linewidth of the EPR signal for photosensitized nitroxyl radical, increasing solvent polarity. Deuterated solvents enlarge the EPR signal intensity in a dose-dependent manner. No EPR signal increase was observed in xanthine-xanthine oxidase reaction or KO2 systems, indicating that TEMP does not react with the superoxide anion. Thus, reaction of TEMP with 1O2 is highly specific.
Biochem Mol Biol Int 1995 Oct
PMID:The specificity and product of quenching singlet oxygen by 2,2,6,6-tetramethylpiperidine. 867 11

The enzyme 6-phosphogluconate dehydratase has been isolated in a stable form by a simple one-step procedure using dye ligand chromatography. The role of metal ions in the activity and stability of the enzyme was investigated. As with aconitase and several other dehydratase enzymes, the active site includes an Fe4S4 cluster. In addition, the purified enzyme has been shown to contain one manganese ion per subunit, which is also essential for activity. Rapid inactivation by superoxide radical was observed, which could only partly be protected by manganous ions The purified enzyme could be stabilised by alpha-glycerophosphate in place of manganese; glycerophosphate mimics the carbon atoms 4 to 6 of the natural substrate. This suggests that the manganous ion may involved in binding this part of the substrate.
Biochem Mol Biol Int 1996 Apr
PMID:6-phosphogluconate dehydratase from Zymomonas mobilis: an iron-sulfur-manganese enzyme. 872 8


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