UNIPROT:P30536 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alloxan participation in extracellular redox processes results in the formation of the reactive oxygen species (ROS) superoxide anions (O2-), hydroxyl radical (OH.) and hydrogen peroxide (H2O2), causing cell damage through a number of complex interactions probably involving several different cellular structures. These involve the plasma membrane, and we have recently presented evidence for lysosomal interference. The present study elucidates the early (within 15 min) events in a model system of macrophage-like cells (J-774) in culture. Addition of 2 mM alloxan and 1 mM cysteine to the medium surrounding the cells (phosphate-buffered saline, PBS, 37 degrees C, pH 7.4) resulted in rapid lysosomal membrane damage with disappearance of the proton gradient as visualized by acridine orange relocalization, as well as plasma membrane alterations leading to increased leakage of fluorescein after fluorescein diacetate staining. These events were later (greater than 30 min) followed by cellular degeneration in the form of blebbing. Mitochondrial damage (rhodamine 123 relocalization) was a late event. Cells pretreated with desferrioxamine (Des) and superoxide dismutase (SOD) or Des, SOD and catalase (CAT) to induce partial (H2O2 formation only) or almost full protection (no ROS formation) showed about the same reactions as when cells were exposed to alloxan and cysteine without scavengers (O2-, H2O2 and OH. formation) or with PBS only, respectively. The results are interpreted as indicating that the cytotoxicity is a consequence mainly of H2O2 involvement and probably of lysosomal influx of H2O2 with ensuing OH.formation within secondary lysosomes containing trace amounts of reactive iron. It is suggested that the resultant lysosomal membrane damage is followed by leakage of lysosomal hydrolases and ensuing cellular degeneration.
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PMID:Extracellular reduction of alloxan results in oxygen radical-mediated attack on plasma and lysosomal membranes. 158 Oct 40

Cigarette smoke has been reported to contain free radicals and free radical generators in both the gas and particulate phases. Studies in our laboratory have shown that both cigarette smoke condensate (CSC) and smoke bubbled through phosphate buffered saline solution (smoke-PBS) increased sister chromatid exchanges (SCE) in Chinese hamster ovary cells in a dose-dependent manner. Since oxygen free radicals have been shown to cause SCEs and other chromosomal damage, we investigated the role of these radicals in the induction of SCEs by CSC and smoke-PBS. Addition of the antioxidant enzymes catalase and superoxide dismutase or the oxygen-radical scavenger ascorbic acid failed to reduce the SCE frequency in the presence of either CSC or smoke-PBS. Additional studies indicated that the quantity of hydrogen peroxide produced in CSC or smoke-PBS is too small to account for the observed SCE induction. It appears, therefore, that SCE induction by CSC or smoke-PBS does not involve the participation of oxygen free radicals.
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PMID:Role of oxygen free radicals in the induction of sister chromatid exchanges by cigarette smoke. 264 5

In the present study we have assayed antioxidant enzymatic activities of SOD, CAT, GSH-Px, GSH-Red, and G6PD in erythrocytes from two children with hemolytic-uremic syndrome (HUS) during the acute phase of the disease and after their recovery; in addition, we have tested the percentage of hemolysis after 24-h incubation in PBS containing glucose (1 g/1000 mL) or in the presence of their own plasma. Endogenous plasmatic MDA levels were also evaluated as lipid peroxidation marker. A significant decrease in SOD activity was found in erythrocytes from HUS patients, and the addition of their own plasma further decreased SOD activity. Elevated percentage of hemolysis was found in HUS patients when RBCs were incubated in their own plasma; this last effect was less evident in PBS + glucose.
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PMID:Impaired antioxidant defense mechanisms in two children with hemolytic-uremic syndrome. 821 May 65

Cu/Zn-superoxide dismutase (Cu/Zn-SOD) has been shown to modulate the autoxidation of a variety of phenoic compounds, including 1,4-hydroquinone (HQ), a benzene-derived metabolite. The acceleration of autoxidation of HQ by Cu/Zn-SOD results in the production of 1,4-benzoquinone (BQ). It has been proposed that the chemical mechanism involved in the Cu/Zn-SOD-catalyzed autoxidation of HQ may be occur through either its conventional activity as a superoxide:superoxide oxidoreductase or as a semiquinone:superoxide oxidoreductase. However, Cu/Zn-SOD-accelerated oxidation of HQ has not been resolved experimentally. In this study, with ESR spectroscopy we investigated further the chemical reactions involved in the SOD-accelerated oxidation of HQ. In phosphate-buffered saline (PSB), HQ underwent a slow autoxidation to BQ, which was accelerated by Cu/Zn-SOD, Mn-SOD, or Fe-SOD with similar efficiency. In contrast, among free metals, only Cu(II) strongly mediated the oxidation of HQ to BQ. Mn(II) exhibited a slight capacity to oxidize HQ, whereas neither FE(II) nor FE(III) was capable of modulating the autoxidation of HG. The presence of either form of SOD also dramatically enhanced the formation of semiquinone anion radicals SQ-. from HQ. The SOD-accelerated oxidation of HQ was also accompanied by the generation of H202. In PBS containing bovine serum albumin (BSA) (PBS/BSA), HQ did not undergo autoxidation to SQ-., and as such the presence of SOD was unable to induce the formation of either SQ-. or BQ or the consumption of O2. The addition of 10 microM BQ to HQ (100 or 1000 microM) in PBS/BSA resulted in the formation of SQ-. and initiated a slow rate of oxidation of HQ to BQ. In this case, the presence of Cu/Zn-SOD strongly accelerated the oxidation of HQ to SQ-. and BQ and the utilization of O2. Furthermore, the enhancement by Cu/Zn-SOD of the generation of SQ-. or BQ from HQ in PBS/BSA was extensively inhibited under anaerobic conditions. The enhancement of SQ-. generation from HQ by all three forms of SOD does not support the possibility that Cu/Zn-SOD can oxidize SQ-. to BQ. Taken together, this study demonstrates that unlike free copper, Cu/Zn-SOD does not directly interact with HQ to cause its oxidation to BQ. Rather, the autoxidation of HQ to SQ-. is a prerequisite for the enhancing capacity of Cu/Zn-SOD, and the dismutation of superoxide anion radicals generated from the SQ-. in the presence of O2 appears to be the underlying mechanism responsible for the enhancement by Cu/Zn-SOD of the oxidation of HQ.
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PMID:Role of Cu/Zn-superoxide dismutase in xenobiotic activation. I. Chemical reactions involved in the Cu/Zn-superoxide dismutase-accelerated oxidation of the benzene metabolite 1,4-hydroquinone. 864 79

The membrane permeability and intracellular fate of ([N,N'-bis(2 pyridyl-phenyl-methylene)-1,4-butanediamine](N,N ',N",N"')-copper(II))-diperchlorate (CuPuPhePy), a copper-diSchiff-base complex of superoxide dismutase(SOD)-mimetic activity surviving biochelation, were examined using rat hepatocytes. Lipophilicity was quantified by determining the octanol/water partition coefficients (K(p)) employing PBS as the aqueous phase. K(p)(octanol/water) was close to 1 (0.7 +/- 0.31) for Cu-PuPhePy. The complex associates with phosphatidylcholine liposomes, as deduced from ultracentrifugation and gel filtration experiments. The ability of the complex to permeate cellular membranes was proven by correlating copper release and viability of rat hepatocytes preincubated with CuPuPhePy and treated with digitonin and diethylmaleate (DEM), respectively. The toxicity and reactivity of CuPuPhePy (LD (50) approximately 10 muM for rat hepatocytes under the given conditions) were higher than those of CuSO (4)(LD(50) approximately 16 mu M) and CuZn-SOD (no toxicity in the tested range of concentration). Unlike CuSO(4) and CuZn-SOD, the toxicity and reactivity of the diSchiff-base complex were increased (LD(50) approximately 5 muM) when the concentration of intracellular glutathione was reduced to 16% of the initial content, by preincubating the cells with DEM. The toxicity of Cu-PuPhePy paralleled lipid peroxidation. This phenomenon was strongly enhanced when Cu-PuPhePy and cumene hydroperoxide (CumOOH) were simultaneously allowed to react with rat hepatocytes. This effect was intensified following preincubation with DEM. A decline in Cu(II)-EPR signals was indicative of the reduction of CuPuPhePy by GSH and liver extract, respectively. The concomitant formation of the Cu(I)-GSH complex during this reduction was monitored by the formation of luminescent Cu(I)-thiolate chromophores.
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PMID:Reactivity of lipophilic diSchiff-Base coordinated copper in rat hepatocytes. 865 42

The lethal effect of near ultraviolet (NUV) with low intensity on cultured RPE cells has been investigated. RPE cultures with various cell densities were exposed to NUV (peaking at 365 nm) with or without ambient oxygen in phenol-red-free Dulbecco's PBS containing Ca2+, Mg2+ and glucose (PBS+). The cell viability was determined by dye exclusion and was expressed as cell death ratio (CDR, dead cells/total cells). When RPE cells at 5 x 10(3) cells/cm2, a non-contact low density, were irradiated either at a fixed irradiance (900 microW/cm2) with different exposure times (4 to 8h) or vice versa (8 h with irradiance from 430 to 900 microW/cm2), the change of CDR represented a similar linear function. The replotted data from both the time- and the irradiance-dependent curves indicated that the killing of RPE cells is dependent on the total energy dose of NUV. When a single NUV energy (19.44 J/cm2) was used, CDR was RPE cell density dependent. At confluence, NUV at the highest dosage tested (26 J/cm2) did not show any lethality. An oxygen-free condition abolished the NUV lethality on RPE cells even though the RPE cells were at a non-contact state. The presence of an antioxidant enzyme, catalase, in oxygen-saturated PBS+ protected RPE cells against NUV killing, but superoxide dismutase did not protect the RPE cells against NUV killing. These findings demonstrate that NUV possesses a lethal effect on RPE cells in vitro. Two key factors determine the magnitude and nature of this lethal effect: first, total NUV energy dose determines the nature of NUV's lethal effect; second, RPE growth conditions suggest the importance of cell-cell interaction in protecting these cells from NUV injury. Because an oxygen-free condition abolishes NUV lethality, it suggests that the oxidative stress is directly related to NUV lethal action. The selective inhibition by catalase of NUV killing of RPE cells suggests that the killing is oxidative species specific. NUV radiation might be highly risky to RPE viability in vivo, especially when the integrity of the RPE layer has been lost.
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PMID:Characterization of lethal action of near-ultraviolet on retinal pigment epithelial cells in vitro. 897 37

Previous studies have shown that exposure of Swiss 3T3 cells to mainstream cigarette smoke (CS) trapped in phosphate-buffered saline (smoke-bubbled PBS) resulted in the expression of stress response genes, i.e. haem oxygenase and c-fos, partial inhibition of protein phosphatases 1 and 2A, as well as partial depletion of the cellular glutathione (GSH) pool. Using c-fos gene expression in Swiss 3T3 cells as an indicator for a cellular response against oxidative stress, the following observations are consistent with peroxynitrite as an active principal formed by CS in aqueous solutions: (i) sustained c-fos expression was obtained for smoke-bubbled PBS, peroxynitrite itself and a compound known to stoichiometrically release superoxide and nitric oxide (NO) (3-morpholino-sydnonimine, SIN-1); (ii) c-fos expression in cells exposed to aqueous smoke fractions was inhibited by either the superoxide-scavenging enzyme superoxide dismutase (SOD), in combination with catalase, or the NO-scavenger oxyhaemoglobin (HbO2); and (iii) activation of guanylate cyclase in rat lung cells was observed only when bubbling was performed with filtered smoke and with whole smoke in the presence of SOD/catalase. These results are consistent with a rapid NO-consuming reaction coupled with superoxide-generating properties of the particulate phase of CS. Moreover, (iv) the half-life of the c-fos-inducing activity in smoke-bubbled PBS was found to be <1 h which can be explained by a sustained peroxynitrite formation. Finally, depletion of intracellular thiol levels by smoke-bubbled PBS appears to favour the activation of a redox-sensitive component of the c-fos-inducing pathway.
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PMID:Evidence for peroxynitrite as an oxidative stress-inducing compound of aqueous cigarette smoke fractions. 905 21

Cyclophosphamide (CP) causes lung toxicity in animals and humans. The mechanisms of pulmonary damage caused by CP are not fully understood. Possibilities include direct toxicity to pulmonary tissue or indirect toxicity through activation of pulmonary inflammatory cells. The aim of the present study was the ultrastructural analysis (in transmission electron microscope) of the changes following CP administration within the structures forming the interalveolar septum of the lungs, particularly type II epithelial cells. An attempt was also made to reveal a correlation between the morphological changes, intensity of lipid peroxidation in lung tissue homogenates and blood serum collected from the left ventricle of the heart and the alterations in the activities of superoxide dismutase (Cu, Zn-SOD) and glutathione reductase (GSSG-R). The experiment used 40 male Wistar rats of 160-180 g body weight (b.w.). The animals were divided into two groups. Group I - (20 animals) were given single intraperitoneal (i.p.) dose of 150 mg CP/1 kg b.w./1 ml PBS. Group II - (20 animals) were given single i.p. dose of 1 ml PBS. All experimental animals were sacrificed after 1 (subgroups I, II-1) and 7 (subgroups I, II-7) days of CP (or PBS) treatment. I.p. administration of CP caused an increase in lipid peroxidation products (MDA-malondialdehyde) in lung tissue homogenates especially in subgroup I-1 (p = 0.00174). No statistical differences, however, were noted in the blood serum MDA levels, although a statistically significant decrease was found in GSSG-R (p = 0.00174) and SOD (p = 0.00174) activities in the serum. The paper discusses a potential link between the findings of biochemical analysis and the morphological changes found within lung tissue. Pulmonary trombopoesis was indicated as a possible mechanism preventing a decrease in blood platelet count following CP administration.
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PMID:Cyclophosphamide-induced generation of reactive oxygen species. Comparison with morphological changes in type II alveolar epithelial cells and lung capillaries. 968 51

Dichlorosilicon phthalocyanine (Cl2SiPc) and bis(tri-n-hexylsiloxy) silicon phthalocyanine (HexSiPc) have been evaluated in vitro as potential photosensitizers for photodynamic therapy (PDT) against the human amelanotic melanoma cell line M6. Each photosensitizer is dissolved in a solvent-PBS mixture, or entrapped in egg-yolk lecithin liposomes or in Cremophor EL micelles. The cells are incubated for 1 h with the sensitizer and then irradiated for 20 min, 1 h or 2 h (lambda > 480 nm, 10 mW cm-2). The photocytotoxic effect is dependent on the photosensitizer concentration and the light dose. Higher phototoxicity is observed after an irradiation of 2 h: treatment with a solution of photosensitizer (2 x 10(-9) M) leads to 10% (HexSiPc in egg-yolk lecithin liposomes) or 20% (Cl2SiPc in DMF-PBS solution) cell viability. After 1 h incubation and 20 min of light exposure, the photodynamic effect is connected with the type of delivery system used. For HexSiPc, lower cell viability is found when this photosensitizer is entrapped in egg-yolk lecithin instead of solvent-PBS or for Cremophor EL micelles with Cl2SiPc. Liposome-delivered HexSiPc leads to lipid damage in M6 cells, illustrated by an increase of thiobarbituric acid-reacting substances (TBARs), but the change is not significant with Cremophor EL. The same is observed for the antioxidative defences after photodynamic stress. The cells irradiated with HexSiPc entrapped in liposomes display an increase of superoxide dismutase (SOD) activity and a decrease of glutathione (GSH) level, glutathione peroxidase (GSHPx) and catalase (Cat) activities.
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PMID:Photodynamic activities of silicon phthalocyanines against achromic M6 melanoma cells and healthy human melanocytes and keratinocytes. 1020 78

Experimental melanin protein-induced uveitis (EMIU) is an autoimmune uveitis induced by immunization with uveal melanin protein. Fas and FasL enhancement is reported in rats with EMIU. Tricyclodecan-9-yl-xanthogenate (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C, inhibits inducible nitric oxide synthase (iNOS) induction. In two independent experiments, 35 Lewis rats with EMIU received either D609 or PBS daily. The eyes and draining lymph nodes were collected for histology, analyses of nitrite, peroxide, and superoxide dismutase, Fas and FasL immunochemistry, in situ hybridization for iNOS mRNA and in situ apoptosis detection at the peak of the disease. Both experiments showed significant inhibition of EMIU by D609. Decreases in nitrite and peroxide, increase of superoxide dismutase and lower expressions of iNOS mRNA were found in D609-treated, as compared to PBS-treated eyes. There was mild enhancement of Fas and FasL in the eyes and lymph nodes of D609-injected animals. DNA fragmentation was increased in the lymph nodes of D609-treated rats. We conclude that iNOS activation is responsible for NO production in eyes with EMIU. The suppressive effect of D609 on EMIU may result from scavenging NO and activating apoptosis previously inhibited by NO along with other anti-inflammatory effects.
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PMID:Inhibition of experimental melanin protein-induced uveitis (EMIU) by targeting nitric oxide via phosphatidylcholine-specific phospholipase C. 1047 88

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