Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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Nonhost resistance of cereals to inappropriate formae speciales of Blumeria graminis is little understood. However, on the microscopic level, nonhost defense to B. graminis is reminiscent of host defense preventing fungal development by penetration resistance and the hypersensitive cell death response (HR). We analyzed histochemically the accumulation of superoxide anion radicals (O2*-) and hydrogen peroxide (H2O2) at sites of B. graminis attack in nonhost barley and wheat. Superoxide visualized by subcellular reduction of nitroblue tetrazolium accumulated in association with successful fungal penetration in attacked cells and in cells neighboring HR. In contrast, H2O2 accumulated in cell wall appositions beneath fungal penetration attempts or in the entire epidermal cell during HR. The data provide evidence for different roles and sources of superoxide and H2O2 in the nonhost interaction of cereals with inappropriate formae speciales of B. graminis.
Mol Plant Microbe Interact 2004 Mar
PMID:Superoxide and hydrogen peroxide play different roles in the nonhost interaction of barley and wheat with inappropriate formae speciales of Blumeria graminis. 1500 Mar 97

A promoter (sufAp), inducible by various oxidants, directs transcription of the sufABCDSE operon encoding an alternative Fe-S cluster assembly system in Escherichia coli. Superoxide generators and H2O2 induced expression of sufA-lacZ even in DeltasoxRS and DeltaoxyR mutants, suggesting participation of an additional regulator(s) in oxidant induction of the sufA operon. Through deletion and linker scanning mutagenesis, we found three cis-acting oxidant-responsive elements (OREs). ORE-I lies between -236 and -197 nucleotides from the transcription start site, overlapping extensively with the OxyR binding site reported previously. ORE-II (-156 to -127) was found to be the site of IHF action. ORE-III (-56 to -35) had no predictable binding sites for known regulators. Gel mobility shift assays with a 50 bp DNA probe containing ORE-III revealed the presence of an ORE-III-specific factor that binds only when cells are treated with oxidants. S1 mapping analysis revealed that phenazine methosulphate (PMS) and H2O2 induced sufA expression by more than 40-fold. In a DeltaoxyR mutant, sufA was still induced more than 10-fold. Fur, a ferric uptake regulator that negatively regulates this operon in response to iron availability, did not mediate the oxidant induction. Deletion of the suf operon caused cells to be more sensitive to superoxide-generating agents without affecting sensitivity to H2O2. From these results, we propose that the oxidant induction of the sufA operon is mediated through OxyR, IHF, plus an unidentified oxidant-responsive factor, and that the suf gene products are needed to defend cells against oxidative stress caused by superoxide generators.
Mol Microbiol 2004 Mar
PMID:Induction of the sufA operon encoding Fe-S assembly proteins by superoxide generators and hydrogen peroxide: involvement of OxyR, IHF and an unidentified oxidant-responsive factor. 1500 99

The scavenging activity of three fulvic acids (named XWCS-1, XWCS-4, and XWCS-8 according to time taken for ozonolysis) obtained by ozonolysis of humic acid extracted from Xinjiang (China) weathered coal and a fulvic acid (named XWCFA) extracted from the same coal towards reactive oxygen species such as superoxide radical (O(2)(.)(-)) and hydroxyl radical ((.)OH) was investigated with an electron spin resonance (ESR)-spin trapping method using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) as a spin trap. O(2)(.)(-) was generated with a hypoxanthine-xanthine oxidase system. (.)OH was generated by three different methods; (i) FeSO(4)-hydrogen peroxide (H(2)O(2)) system, (ii) Cu(en)(2)-H(2)O(2) system, and (iii) UVB photolysis of H(2)O(2). At physiological pH, XWCS-1 had the greatest O(2)(.)(-) scavenging activity, followed by XWCS-4, XWCS-8 and XWCFA. XWCFA had the greatest ?OH scavenging activity among the four fulvic acids, whereas XWCS-1 and XWCS-4 enhanced the production of (.)OH from a metal-catalyzed hydroxyl radical generating system, suggesting that these molecules act as prooxidants in the presence of metal ion.
Spectrochim Acta A Mol Biomol Spectrosc 2004 Sep
PMID:Reactive oxygen species scavenging ability of a new compound derived from weathered coal. 1529 33

Superoxide dismutases (SODs) catalyze the dismutation of superoxide radicals to O2 and H2O2 and thus represent a primary line of antioxidant defense in all aerobic organisms. H2O2 is a signal molecule involved in the plant's response to pathogen attack and other stress conditions as well as in nodulation. In this work, we have tested the hypothesis that SODs are a source of H2O2 in indeterminate alfalfa (Medicago sativa) and pea (Pisum sativum) nodules. The transcripts and proteins of the major SODs of nodules were localized by in situ RNA hybridization and immunogold electron microscopy, respectively, whereas H2O2 was localized cytochemically by electron microscopy of cerium-perfused nodule tissue. The transcript and protein of cytosolic CuZnSOD are most abundant in the meristem (I) and invasion (II) zones, interzone II-III, and distal part of the N2-fixing zone (III), and those of MnSOD in zone III, especially in the infected cells. At the subcellular level, CuZnSOD was found in the infection threads, cytosol adjacent to cell walls, and apoplast, whereas MnSOD was in the bacteroids, bacteria within infection threads, and mitochondria. The distinct expression pattern of CuZnSOD and MnSOD suggests specific roles of the enzymes in nodules. Large amounts of H2O2 were found at the same three nodule sites as CuZnSOD but not in association with MnSOD. This colocalization led us to postulate that cytosolic CuZnSOD is a source of H2O2 in nodules. Furthermore, the absence or large reduction of H2O2 in nodule tissue preincubated with enzyme inhibitors (cyanide, azide, diphenyleneiodonium, diethyldithiocarbamate) provides strong support to the hypothesis that at least some of the H2O2 originates by the sequential operation of an NADPH oxidase-like enzyme and CuZnSOD. Results also show that there is abundant H2O2 associated with degrading bacteroids in the senescent zone (IV), which reflects the oxidative stress ensued during nodule senescence.
Mol Plant Microbe Interact 2004 Dec
PMID:Localization of superoxide dismutases and hydrogen peroxide in legume root nodules. 1559 35

Superoxide has been shown to be critical for hippocampal long-term potentiation (LTP) and hippocampus-dependent memory function. A possible source for the generation of superoxide during these processes is NADPH oxidase. The active oxidase consists of two membrane proteins, gp91phox and p22phox, and four cytosolic proteins, p40phox, p47phox, p67phox, and Rac. Upon stimulation, the cytosolic proteins translocate to the membrane to form a complex with the membrane components, which results in production of superoxide. Here, we determined the presence, localization, and functionality of a NADPH oxidase in mouse hippocampus by examining the NADPH oxidase proteins as well as the production of superoxide. All of the NADPH oxidase proteins were present in hippocampal homogenates and enriched in synaptoneurosome preparations. Immunocytochemical analysis of cultured hippocampal neurons indicated that all NADPH oxidase proteins were localized in neuronal cell bodies as well as dendrites. Furthermore, double labeling analysis using antibodies to p67phox and the presynaptic marker synaptophysin suggest a close association of the NADPH oxidase subunits with synaptic sites. Finally, stimulation of hippocampal slices with phorbol esters triggered translocation of the cytoplasmic NADPH oxidase proteins to the membrane and an increase in superoxide production that was blocked by inhibitors of NADPH oxidase. Taken together, our data suggest that NADPH oxidase is present in mouse hippocampus and might be the source of superoxide production required for LTP and memory function.
Mol Cell Neurosci 2005 May
PMID:Synaptic localization of a functional NADPH oxidase in the mouse hippocampus. 1586 50

Excessive free radical formation has been implicated as one of the causative factors in neurotoxic damage associated with variety of metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-dependent neurotoxicity remains far from clear, overwhelming data give credence to a mediatory role for astrocytes, a major cell type that preferentially accumulates MeHg. To extend our recent findings of MeHg-induced increase in ROS formation (G. Shanker, J.L. Aschner, T. Syversen et al., Free radical formation in cerebral cortical astrocytes in culture induced by methylmercury, Mol. Brain Res. 128 (2004) 48-57), the present studies were designed to assess the effect of modulating intracellular glutathione (GSH) content, on ROS generation, in the absence and presence of MeHg. Intracellular GSH was reduced by treatment with 100 microM buthionine-L-sulfoxane (BSO) for 24 h, and increased by treatment with 1 mM l-2-oxothiazolidine-4-carboxylic acid (OTC) for 24 h. Additionally, the effects of the selective antioxidants, catalase (1000 U/ml for 1 h), an H2O2 scavenger, and n-propyl gallate (100 microM for 1 h), a superoxide radical (*O2-) and possibly hydroxyl radical (*OH) scavenger on MeHg-induced ROS formation were examined. After these treatments, astrocytes were exposed to +/-10 microM MeHg for 30 min, following which the fluorescent probes, CM-H2DCFA and CM-H2XRos were added; 20 min later, laser scanning confocal microscopy (LSCM) images were obtained. Exposure of astrocytes for 24 h to 100 microM BSO, a GSH synthesis inhibitor, led to a significant increase in mitochondrial ROS (i.e., *O2-, *NO, and ONOO-) formation, as assessed with CM-H2XRos mitotracker red dye. Similarly, BSO increased ROS formation in various intracellular organelles, as assessed with CM-H2DCFDA. BSO in combination with MeHg increased fluorescence levels in astrocytes to levels above those noted with BSO or MeHg alone, but this effect was statistically indistinguishable from either of these groups (BSO or MeHg). Pretreatment of astrocytes for 24 h with 1 mM OTC abolished the MeHg-induced increase in ROS. Results similar to those obtained with OTC were observed with the free radical scavenger, n-propyl gallate (n-PG). The latter had no significant effects on astrocytic fluorescence when administered alone. This *O2- and possibly *OH radical scavenger significantly attenuated MeHg-induced ROS formation. Catalase, an H2O2 scavenger, was less effective in reducing MeHg-induced ROS formation. Taken together, these studies point to the important protective effect of adequate intracellular GSH content as well as antioxidants against MeHg-triggered oxidative stress in primary astrocyte cultures.
Brain Res Mol Brain Res 2005 Jun 13
PMID:Modulatory effect of glutathione status and antioxidants on methylmercury-induced free radical formation in primary cultures of cerebral astrocytes. 1595 Jul 56

Mercury is a highly toxic metal which induces oxidative stress. Superoxide dismutases, catalase, and glutathion peroxidase are proteins involved in the endogenous antioxidant defence system. In the present study rats were administered orally, by gavage, a single daily dose of HgCl2 for three consecutive days. In order to find a relation between the proteins involved in the antioxidant defence and mercury intoxication, parameters of liver injury, redox state of the cells, as well as intracellular protein levels and enzyme activities of Mn-dependent superoxide dismutase (MnSOD), Cu-Zn-dependent superoxide dismutase (CuZnSOD), catalase, and glutathione peroxidase (GPx) were assayed both in blood and in liver homogenates. HgCl2 at the doses of 0.1 mg/kg produced liver damage which that was detected by a slight increase in serum alanine aminotransferase and gamma glutamyl transferase. Hepatic GSH/GSSG ratio was assayed as a parameter of oxidative stress and a significant decrease was detected, as well as significant increases in enzyme activities and protein levels of hepatic antioxidant defence systems. Changes in both MnSOD and CuZnSOD were parallel to those of liver injury and oxidative stress, while the changes detected in catalase and GPx activities were progressively increased along with the mercury intoxication. Other enzyme activities related to the glutathione redox cycle, such as glutathione reductase (GR) and glucose-6-phosphate dehydrogenase (G6PDH), also increased progressively. We conclude that against low doses of mercury that produce a slight oxidative stress and liver injury, the response of the liver was to induce the synthesis and activity of the enzymes involved in the endogenous antioxidant system. The activities of all the enzymes assayed showed a rapidly induced coordinated response.
J Biochem Mol Toxicol 2005
PMID:Endogenous antioxidant defence system in rat liver following mercury chloride oral intoxication. 1597 96

The present study reports the radioprotective properties of a hydro-alcoholic rhizome extract of Rhodiola imbricata (code named REC-7004), a plant native to the high-altitude Himalayas. The radioprotective effect, along with its relevant superoxide ion scavenging, metal chelation, antioxidant, anti-lipid peroxidation and anti-hemolytic activities was evaluated under both in vitro and in vivo conditions. Chemical analysis showed the presence of high content of polyphenolics (0.971 +/- 0.01 mg% of quercetin). Absorption spectra analysis revealed constituents that absorb in the range of 220-290 nm, while high-performance liquid chromatography (HPLC) analysis confirmed the presence of four major peaks with retention times of 4.780, 5.767, 6.397 and 7.577 min. REC-7004 was found to lower lipid oxidation significantly (p < 0.05) at concentrations viz., 8 and 80 microg/ml respectively as compared to reduced glutathione, although the optimally protective dose was 80 microg/ml, which showed 59.5% inhibition of induction of linoleic acid degradation within first 24 h. The metal chelation activity of REC-7004 was found to increase concomitantly from 1 to 50 microg/ml. REC-7004 (10-50 microg/ml) exhibited significant metal chelation activity (p < 0.05), as compared to control, and maximum percentage inhibition (30%) of formation of iron-2,2'-bi-pyridyl complex was observed at 50 microg/ml, which correlated well with quercetin (34.9%), taken as standard. The reducing power of REC-7004 increased in a dose-dependent manner. The absorption unit value of REC-7004 was significantly lower (0.0183 +/- 0.0033) as compared to butylated hydroxy toluene, a standard antioxidant (0.230 +/- 0.091), confirming its high reducing ability. Superoxide ion scavenging ability of REC-7004 exhibited a dose-dependent increase (1-100 microg/ml) and was significantly higher (p < 0.05) than that of quercetin at lower concentrations (1-10 microg/ml), while at 100 microg/ml, both quercetin and REC-7004 scavenged over 90% superoxide anions. MTT assay in U87 cell line revealed an increase in percent survival of cells at doses between 25 and 125 microg/ml in case of drug + radiation group. In vivo evaluation of radio-protective efficacy in mice revealed that intraperitoneal administration of REC-7004 (maximally effective dose: 400 mg/kg b.w.) 30 min prior to lethal (10 Gy) total-body gamma-irradiation rendered 83.3% survival. The ability of REC-7004 to inhibit lipid peroxidation induced by iron/ascorbate, radiation (250 Gy) and their combination [i.e., iron/ascorbate and radiation (250 Gy)], was also investigated and was found to decrease in a dose-dependent manner (0.05-2 mg/ml). The maximum percent inhibition of formation of MDA-TBA complex at 2 mg/ml in case of iron/ascorbate, radiation (250 Gy) and both i.e., iron/ascorbate with radiation (250 Gy) was 53.78, 63.07, and 51.76% respectively and were found to be comparable to that of quercetin. REC-7004 (1 microg/ml) also exhibited significant anti-hemolytic capacity by preventing radiation-induced membrane degeneration of human erythrocytes. In conclusion, Rhodiola renders in vitro and in vivo radioprotection via multifarious mechanisms that act in a synergistic manner.
Mol Cell Biochem 2005 May
PMID:Evaluation of radioprotective activities Rhodiola imbricata Edgew--a high altitude plant. 1601 56

Superoxide dismutases (SOD), a group of metal-containing enzymes, have a vital anti-oxidant role in human health, conferred by their scavenging of one of the reactive oxygen species, superoxide anion. Three types of SODs are known in humans, with the most abundant being cytosolic SOD1, identified by its Cu, Zn-containing prosthetic group. The presence of these metals and the coordination to certain amino acids are essential for function. SODs are among the first line of defense in the detoxification of products resulting from oxidative stress. Here, we describe the importance of SOD function, and the need for coordination with other ROS-scavenging enzymes in this pathway of detoxification. The impact of metal-deficient diets (copper or zinc) or incorrect metal ion incorporation (copper chaperone for SOD) onto nascent SOD, are also examined. Finally, human pathologies associated with either SOD dysfunction or decreased activity are discussed with current progress on the development of novel therapies.
Mol Aspects Med
PMID:Superoxide dismutases and their impact upon human health. 1609 95

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are highly reactive transient chemical species, which play an important role in the etiology of tissue injury in rheumatoid arthritis (RA). The effects of milk extract of Semecarpus anacardium Linn. nut (SA) was studied on adjuvant arthritis in rats. Arthritis was induced by injecting 0.1 ml of heat killed mycobacterium tuberculosis (10 mg/ml of paraffin oil) intradermally into the left hind paw. A significant increase in the levels of lipid peroxides (LPO), ROS (superoxide radical, hydroxyl radical, H(2)O(2) and myeloperoxidase) and RNS (nitrate+nitrite) observed in adjuvant arthritic animals were found to be significantly decreased on administration of the drug at 150 mg/kg body weight/day. The antioxidant defense system studied in arthritic animals were altered significantly as evidenced by the decrease in antioxidants. Treatment with SA recouped the altered antioxidant defense components to near normal levels. These evidences suggest that the free radical mediated damage during arthritis could have been controlled by SA by its free radical quenching and antioxidative potential.
Mol Cell Biochem 2005 Aug
PMID:Semecarpus anacardium Linn. nut milk extract, an indigenous drug preparation, modulates reactive oxygen/nitrogen species levels and antioxidative system in adjuvant arthritic rats. 1613 90


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