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1.
The embryo of oviparous species is confronted by a highly oxidative stress generating as it grows and must rely on effective antioxidant system for protection. Proteins of avian egg albumin have been suggested to play the major redox-modulatory role during embryo development. Recently, we found that ovotransferrin (OTf) undergoes distinct thiol-linked self-cleavage in a redox-dependent process. In this study, we explore that OTf is SOD mimic protein with a potent superoxide anion (O 2−) scavenging activity. The O 2− scavenging activity was investigated using the natural xanthine/xanthine oxidase (X/XOD) coupling system. OTf exhibited O 2− scavenging activity in a dose-dependent manner and showed remarkably higher scavenging activity than the known antioxidants, ascorbate or serum albumin. The isolated half-molecules of OTf exhibited higher scavenging activity than the intact molecule, whereas the N-lobe showed much greater activity. OTf dramatically quenched the O 2− flux but had no effect on the urate production in the X/XOD system, indicating its unique specificity to scavenge O 2− but not oxidase inhibition. Strikingly, metal-bound OTf exhibited greater O 2− dismutation capacity than the apo-protein, ranging from moderate (Zn 2+-OTf and Fe 2+-OTf) to high (Mn 2+-OTf and Cu 2+-OTf) activity with the Cu 2+-OTf being the most potent scavenger. In a highly sensitive fluorogenic assay, the metal-bound OTf exhibited significant increase in the rate of H 2O 2 production in the X/XOD reaction than the apo-OTf, providing evidence that Zn 2+-, Mn 2+- and Cu 2+-OTf possess SOD mimic activity. This finding is the first to describe that OTf is an O 2− scavenging molecule, providing insight into its novel SOD-like biological function, and heralding a fascinating opportunity for its potential candidacy as antioxidant drug. 相似文献
2.
Crystals of calcium oxalate monohydrate (COM) in the renal tubule form the basis of most kidney stones. Tubular dysfunction resulting from COM-cell interactions occurs by mechanism(s) that are incompletely understood. We examined the production of reactive oxygen intermediates (ROI) by proximal (LLC-PK1) and distal (MDCK) tubular epithelial cells after treatment with COM (25–250 μg/ml) to determine whether ROI, specifically superoxide (O 2•−), production was activated, and whether it was sufficient to induce oxidative stress. Employing inhibitors of cytosolic and mitochondrial systems, the source of ROI production was investigated. In addition, intracellular glutathione (total and oxidized), energy status (ATP), and NADH were measured. COM treatment for 1–24 h increased O 2•− production 3–6-fold as measured by both lucigenin chemiluminescence in permeabilized cells and dihydrorhodamine fluorescence in intact cells. Using selective inhibitors we found no evidence of cytosolic production. The use of mitochondrial probes, substrates, and inhibitors indicated that increased O 2•− production originated from mitochondria. Treatment with COM decreased glutathione (total and redox state), indicating a sustained oxidative insult. An increase in NADH in COM-treated cells suggested this cofactor could be responsible for elevating O 2•− generation. In conclusion, COM increased mitochondrial O 2•− production by epithelial cells, with a subsequent depletion of antioxidant status. These changes may contribute to the reported cellular transformations during the development of renal calculi. 相似文献
3.
In the gingival crevicular fluid (GCF) of control and chronic adult periodontitis (CAP) patients there is a spontaneous release of O 2- radicals from polymorphonuclear leukocytes (PMN). The addition of the exogenous stimuli phorbol myrystate acetate (PMA) decreased the O 2- formation in control GCF, while in CAP patients produced a marked enhancement of O 2- generation.
The circulating PMN of control subjects did not show a spontaneous O 2- formation, differently from CAP patients. On the contrary, a similar O 2- production was measured when the circulating PMN were stimulated with PMA.
Moreover, the antioxidant activity measured in 10μl of cell free gingival supernatant (GS) of control and CAP patients had the same values by inhibiting 12.6% and 18.9% respectively of the O 2- formation supported by a xanthine/xanthine oxidase system.
Probably, the protective or destructive effect of PMN in GCF of CAP patients depends on the variations of the rate of O 2- formation in respect to the intrinsic antioxidant property of GS. 相似文献
4.
Om wild-type Escherichia coli, near-ultraviolet radiation (NUV) was only weakly mutagenic. However, in an allelic mutant strain ( sodA sodB) that lacks both Mn- and Fe-superoxide dismutase (SOD) and assumed to have excess superoxide anion (O 2−), NUV induced a 9-fold increase in mutation above the level that normally occurs in this double mutant. When a sodA sodB double mutant contained a plasmid carrying katG+ HP-I catalase), mutation by NUV was reduced to wild-type ( sodA+ sodB+) levels. Also, in the sodA sodB xthA triple mutant, which lacks exonuclease III (exoIII) in addition to SOD, the mutations frequency by NUV was reduced to wild-type levels. This synergistic action of NUV and O 2− suggested that pre-mutational lesions occur, with exoIII converting these lesions to stable mutants. Exposure to H 2O 2 induced a 2.8 fold increase in mutations in sodA sodB double mutants, but was reduced to control levels when a plasmid carrying katG+ was introduced. These results suggest that NUV, in addition to its other effects on cells, increases mutations indirectly by increasing the flux of OH . radicals, possibly by generating excess H 2O 2. 相似文献
5.
We have previously shown that crystals of calcium oxalate (COM) elicit a superoxide (O 2−) response from mitochondria. We have now investigated: (i) if other microparticles can elicit the same response, (ii) if processing of crystals is involved, and (iii) at what level of mitochondrial function oxalate acts. O 2− was measured in digitonin-permeabilized MDCK cells by lucigenin (10 μM) chemiluminescence. [ 14C]-COM dissociation was examined with or without EDTA and employing alternative chelators. Whereas mitochondrial O 2− in COM-treated cells was three- to fourfold enhanced compared to controls, other particulates (uric acid, zymosan, and latex beads) either did not increase O 2− or were much less effective (hydroxyapatite +50%, p < 0.01), with all at 28 μg/cm 2. Free oxalate (750 μM), at the level released from COM with EDTA (1 mM), increased O 2− (+50%, p < 0.01). Omitting EDTA abrogated this signal, which was restored completely by EGTA and partially by ascorbate, but not by desferrioxamine or citrate. Omission of phosphate abrogated O 2−, implicating phosphate-dependent mitochondrial dicarboxylate transport. COM caused a time-related increase in the mitochondrial membrane potential (Δψ m) measured using TMRM fluorescence and confocal microscopy. Application of COM to Fura 2-loaded cells induced rapid, large-amplitude cytosolic Ca 2+ transients, which were inhibited by thapsigargin, indicating that COM induces release of Ca 2+ from internal stores. Thus, COM-induced mitochondrial O 2− requires the release of free oxalate and contributes to a synergistic response. Intracellular dissociation of COM and the mitochondrial dicarboxylate transporter are important in O 2− production, which is probably regulated by Δψ m. 相似文献
6.
Of production by homogenates and isolated membranes of E. coli has been examined. Approximately one-fourth of the O 2-generated by extracts in the prescence of NAD (P) H is attributable to the membranes. The autoxidizable membrane component is a member of the respiratory chain, since O 2-production is NADH-specific, amplified by cyanide, and absent from membranes lacking the respiratory NADH dehyd-rogenase. Other respiratory substrates (succinate, I -phosphoglycerol, D-lactate. and L-lactate) supported Or production at efficiencies between 3 and 30 O 2-released per 10.000 electrons transferred, under conditions of substrate saturation.
Membranes from quinoneless mutants quantitatively retain the ability to evolve O 2-. indicating that the dehydrogenases are the sites of O 2-production. Relative O 2-production was greater at low substrate concentrations, probably reflecting the facilitation of unpairing of electrons that may occur when enzymes with multiple redox centers are only partially reduced.
Respiration rate, cell volume, rates of membraneous and cytosolic O 2-production, and SOD levels were used to calculate a steady-state concentration of O 2-between 10 -- 10 and 10 -- 9 M in well-fed, aerobic, SOD-proficient cells. 相似文献
7.
Hydrogen peroxide, produced by inflammatory and vascular cells, induces oxidative stress that may contribute to endothelial dysfunction. In smooth muscle cells, H 2O 2 induces production of O 2− by activating NADPH oxidase. However, the mechanisms whereby H 2O 2 induces oxidative stress in endothelial cells are poorly understood. We examined the effects of H 2O 2 on O 2− levels on porcine aortic endothelial cells (PAEC). Treatment with 60 μmol/L H 2O 2 markedly increased intracellular O 2− levels (determined by conversion of dihydroethidium to hydroxyethidium) and produced cytotoxicity (determined by propidium iodide staining) in PAEC. Overexpression of human manganese superoxide dismutase in PAEC reduced O 2− levels and attenuated cytotoxicity resulting from treatment with H 2O 2. L-NAME, an inhibitor of nitric oxide synthase (NOS), and apocynin, an inhibitor of NADPH oxidase, reduced O 2− levels in PAEC treated with H 2O 2, suggesting that both NOS and NADPH oxidase contribute to H 2O 2-induced O 2− in PAEC. Inhibition of NADPH oxidase using apocynin and NOS rescue with L-sepiapterin together reduced O 2− levels in PAEC treated with H 2O 2 to control levels. This suggests interaction-distinct NOS and NADPH oxidase pathways to superoxide. We conclude that H 2O 2 produces oxidative stress in endothelial cells by increasing intracellular O 2− levels through NOS and NADPH oxidase. These findings suggest a complex interaction between H 2O 2 and oxidant-generating enzymes that may contribute to endothelial dysfunction. 相似文献
8.
1. Rate constants for reduction of paraquat ion (1,1′-dimethyl-4,4′-bipyridy-lium, PQ 2+) to paraquat radical (PQ +·) by e−aq and CO 2−· have been measured by pulse radiolysis. Reduction by e−aq is diffusion controlled ( k = 8.4·10 10 M −1·s −1) and reduction by CO 2−· is also very fast k = 1.5·10 10 M −1·s −1). 2. The reaction of paraquat radical with oxygen has been analysed to give rate constants of 7.7·108 M−1·s−1 and 6.5·108 M−1·s−1 for the reactions of paraquat radical with O2 and O2−·, respectively. The similarity in these rate constants is in marked contrast to the difference in redox potentials of O2 and O2−· (− 0.59 V and + 1.12 V, respectively). 3. These rate constants, together with that for the self-reaction of O2−·, have been used to calculate the steady-state concentration of O2−· under conditions thought to apply at the site of reduction of paraquat in the plant cell. On the basis of these calculations the decay of O2−· appears to be governed almost entirely by its self-reaction, and the concentration 5 μm away from the thylakoid is still 90% of that at the thylakoid itself. Thus, O2−· persists long enough to diffuse as far as the chloroplast envelope and tonoplast, which are the first structures to be damaged by paraquat treatment. O2−· is therefore sufficiently long-lived to be a candidate for the phytotoxic product formed by paraquat in plants. 相似文献
9.
Trehalose is known to protect membranes and macromolecules. Its accumulation has been implicated in allowing plants to tolerate stress, including heat-shock. However, under heat-shock, it is not clear whether trehalose eliminates reactive oxygen species (ROS) directly or indirectly by protecting antioxidant enzymes. In this study, we initially examined the effects of trehalose on the activities of key antioxidant enzymes, including superoxide dismutases (SODs), ascorbate catalases (CATs), and ascorbate peroxidases (APX) from wheat ( Triticum aestivum L.), and then measured the ability of trehalose to scavenge hydrogen peroxide (H 2O 2) and superoxide anions (O 2−). Our results indicated that trehalose protected SOD activity slightly. However, it inhibited CAT and APX activities under heat stress, with a little protection of CAT activity (only about 7% promotion) at 22 °C. Moreover, trehalose scavenged H 2O 2 and O 2− greatly in a concentration-dependent manner, reaching the maximal scavenging H 2O 2 rate of 95% and O 2− rate of 78%, respectively, at 50 mM trehalose. These results suggest that trehalose plays a direct role in eliminating H 2O 2 and O 2− in wheat under heat stress. 相似文献
10.
1. The effect of H 2O 2 (4.7 × 10 -9 4.7 × 10 -3M) on prostanoid production by isolated glomeruli from normotensive (WKY) and, spontaneously hypertensive rats (SHR) has been studied.
2. Oxidant stress significantly increased synthesis of prostaglandin E 2(PGE 2), I 2(PGI 2)and thromboxane A 2 (TxA 2) by glomeruli from both strains whereas the ratio (PGE 2 + PGI 2)/TxA 2 increased in only SHR.
3. Pre-incubation of glomeruli with the angiotensin converting enzyme inhibitors captopril or lisinopril, had virtually no effect on H 2O 2-induced synthesis of individual prostanoids nor on the ratio (PGE 2 + PGI 2)/TA 2 by glomeruli from either WKY or SHR.
4. The findings suggest that H 2O 2-induced changes in glomerular function may be mediated, in part, by PGs but fail to support the suggestion that the ability of ACEI to protect glomeruli from H 2O 2-induced damage is determined by PGs. 相似文献
11.
The past two decades have witnessed an explosion in our understanding of oxygen toxicity. The discovery of superoxide dismutases (SODs) (EC.1.15.1.1), which specifically catalyze the dismutation of superoxide radicals (O 2−) to hydrogen peroxide (H 2O 2) and oxygen, has indicated that O 2− is a normal and common byproduct of oxygen metabolism. There is an increasing evidence to support the conclusion that superoxide radicals play a major role in cellular injury, mutagenesis, and many diseases. In all cases SODs have been shown to protect the cells against these deleterious effects. Recent advances in molecular biology and the isolation of different SOD genes and SOD c-DNAs have been useful in proving beyond doubt the physiological function of the enzyme. The biosynthesis of SODs, in most biological systems, is under rigorous controls. In general, exposure to increased pO 2, increased intracellular fluxes of O 2−, metal ions perturbation, and exposures to several environmental oxidants have been shown to influence the rate of SOD synthesis in both prokaryotic and eukaryotic organisms. Recent developments in the mechanism of regulation of the manganese-containing superoxide dismutase of Escherichia coli will certainly open new research avenues to better understand the regulation of SODs in other organisms. 相似文献
12.
Phagocytic cells such as neutrophils generate superoxide anions (O 2−) within phagocytic vacuoles for killing and digesting microorganisms. Here we report the simultaneous observation of morphological changes and O 2− generation in single phagocytic cells during phagocytosis. Point stimulation of a cell by contact with an opsonized microelectrode at the cell surface induced significant deformation to engulf the electrode, and also induced the O 2− generation which was measured by the electrode. Periodic fluctuations in the magnitude of the O 2− generation were observed in the time course. These oscillations may be caused by metabolic regulation of the formation of NADPH, which is the substrate for the O 2− generation. 相似文献
13.
Nitrogen dioxide (NO 2•) is a key biological oxidant. It can be derived from peroxynitrite via the interaction of nitric oxide with superoxide, from nitrite with peroxidases, or from autoxidation of nitric oxide. In this study, submicromolar concentrations of NO 2• were generated in < 1 μs using pulse radiolysis, and the kinetics of scavenging NO 2• by glutathione, cysteine, or uric acid were monitored by spectrophotometry. The formation of the urate radical was observed directly, while the production of the oxidizing radical obtained on reaction of NO 2• with the thiols (the thiyl radical) was monitored via oxidation of 2,2′-azino-bis-(3-ethylthiazoline-6-sulfonic acid). At pH 7.4, rate constants for reaction of NO 2• with glutathione, cysteine, and urate were estimated as 2 × 10 7, 5 × 10 7, and 2 × 10 7 M −1 s −1, respectively. The variation of these rate constants with pH indicated that thiolate reacted much faster than undissociated thiol. The dissociation of urate also accelerated reaction with NO 2• at pH > 8. The thiyl radical from GSH reacted with urate with a rate constant of 3 × 10 7 M −1 s −1. The implications of these values are: (i) the lifetime of NO 2• in cytosol is < 10 μs; (ii) thiols are the dominant ‘sink’ for NO 2• in cells/tissue, whereas urate is also a major scavenger in plasma; (iii) the diffusion distance of NO 2• is 0.2 μm in the cytoplasm and < 0.8 μm in plasma; (iv) urate protects GSH against depletion on oxidative challenge from NO 2•; and (v) reactions between NO 2• and thiols/urate severely limit the likelihood of reaction of NO 2• with NO• to form N 2O 3 in the cytoplasm. 相似文献
14.
The oxidation of melatonin (MEL) using the Cu(II) + H 2O 2 + HO − (the Fenton-like reaction) system was investigated by chemiluminescence (CL), fluorescence, spectrophotometric, and EPR spin trapping techniques. The reaction exhibits CL in the 400–730 nm region. The light emission from the Fenton-like reaction was greatly enhanced in the presence of MEL and was strongly dependent on its concentration. The spectrum measured with cut-off filters revealed maxima at around 460, 500, 580–590, 640–650, and 690–700 nm. The band at 460 nm may be due to the excited cleavage product, N 1-acetyl-N 2-formyl-5-methoxykynuramine, whereas the bands at 500, 580–590, 640–650, and 700 nm were similar to those observed for singlet molecular oxygen ( 1O 2). The effect of reactive oxygen species (ROS) scavengers on the light emission was studied. The CL was strongly inhibited by the 1O 2 scavengers in a dose-dependent manner; at concentration 1 mM the potency of 1O 2 scavenging was 5,5-dimethylcyclohexandione-1,3 > methionine > histidine > hydroquinone. The potency of HO • scavenging by thiourea, tryptophan, cysteine at concentration 5 mM was 79–94%, by 1 mM glutathione and trolox 75 and 94%, respectively, and by 10 mM cimetidine 18%. Specific acceptors of O 2•− such as p-nitroblue tetrazolium chloride and 4,5-dihydroxy-1,3-benzene disulfonic acid (tiron) at concentration 5 mM decreased the CL by 51 and 95%, respectively, whereas superoxide dismutase (SOD) does not reduce the emission at concentration 2.8 U/ml. At higher concentration SOD substantially enhanced the light emission. Addition of 1360 U/ml catalase and 100 μM desferrioxamine strongly inhibited CL (96 and 90%, respectively). The increased generation of 1O 2 from the Cu/H 2O 2 system in the presence of MEL was confirmed using the spectrophotometric method based on the bleaching of p-nitrosodimethylaniline and by trapping experiments with 2,2,6,6-tetramethylpiperidine (TEMP) and subsequent electron paramagnetic (EPR) spectroscopy. These findings suggest the increased production of reactive oxygen species (O 2•−, HO •, 1O 2) from the Fenton-like reaction in the presence of MEL. This means that the hormone is not able to act as classical chain-breaking antioxidant even at low concentration, and may show clear prooxidant activity at higher concentrations. In addition, long-lived carbonyl product of the MEL transformation in the triplet state can also be toxic by transferring its energy to organelles and causing a photochemical process. 相似文献
15.
Several studies have demonstrated the involvement of reactive nitrogen and oxygen species (RNOS) in the neurotoxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydro-pyridin (MPTP) and methamphetamine (METH), so the contribution of altered nitric oxide synthase (NOS) enzyme function can be suspected. In this study, about 50% increase in nitric oxide (NO) production in the mouse striatum was found between 4 and 12 h after a single MPTP injection, allowing an increased peroxynitrite (ONOO −) formation in the target brain region. However, METH injection induced a rapid decrease of NO formation both in mouse striatum and hippocampus, reaching its minimum level at 2 h, and restored to the control value after 6 h in the striatum and 12 h in the hippocampus. The uncoupled function of NOS with increased superoxide (O 2−) production after METH injection is suggested. 相似文献
16.
Enhanced oxidative stress due to hyperglycemia has been implicated in diabetic complications and is considered a major cause of cell and tissue damage. The aim of the present study was to investigate whether synthetic manganese porphyrin, Mn(III) 5,10,15,20-tetrakis( N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP 5+) can ameliorate diabetes-induced oxidative stress and affect life span of diabetic rats.
Diabetes was induced by a single (60 mg/kg) intraperitoneal injection of streptozotocin in male Wistar rats. Oxidative stress was monitored by measuring malondialdehyde levels (MDA) in blood plasma and erythrocytes using HPLC. The antioxidant status was assessed by measuring the total radical-trapping potential (TRAP) of blood plasma. Life span of the animals was used as an indication of the overall effect of MnTM-2-PyP 5+. MnTM-2-PyP 5+ was administered subcutaneously at 1 mg/kg for the duration of the experiment, five times/week followed by one week of rest.
Diabetes increased plasma and erythrocyte levels of MDA and decreased TRAP. MnTM-2-PyP 5+ had no effect on blood glucose and glycosylated hemoglobin, but significantly increased TRAP and lowered MDA. This Mn porphyrin decreased mortality and markedly extended the life span of the diabetic animals.
MnTM-2-PyP 5+ suppressed diabetes-induced oxidative stress, which presumably accounts for its beneficial effect on the life span of the diabetic rats. The results indicate that Mn(III) N-alkylpyridylporphyrins can be used as potent therapeutic agents in diabetes. 相似文献
17.
Under physiological pH conditions (pH 7.2-7.4) the rate constant of the reaction NO + O 2 yielding peroxonitrite (ONOO) was determined as k = (3.7 ± 1.1) × 10 7 M 1 s 1. The decay of peroxonitrite at this pH follows first order kinetics with a rate constant of 1.4 s 1. At alkaline pH peroxonitrite is practically stable.
Possible consequences of these reactions for the biological lifetime of EDRF will be discussed. 相似文献
18.
Histochemical localization of superoxide anion (O 2·−) scavenging activity in rat brain was visualized by the tissue-blotting technique. The activity was thought to mainly depend on Cu/Zn-SOD, because the localization of the activity was identical with the immunohistochemistry of Cu/Zn-SOD and the localization of its mRNA in the brain. Moreover, the activity was dramatically decreased after treatment of Cu (I) chelater. The activity was detected in pyramidal cells of the cortex, granular, and mitral cells of the olfactory bulbs, pyramidal cell layer CA1 to CA3, and dentate gyrus of hippocampus formation and granular cells of the cerebellum. Moreover, the activity was detected in the pontine nuclei of brain stem. Olfactory bulbs, hippocampus, and cerebellum were believed to be bestowed high brain functions, i.e., long-term potentiation and long-term depression. A part of the function was regulated by a retrograde neurotransmitter, nitric oxide ( ·NO). Our findings suggest that the SOD is colocalized with NO synthase in olfactory bulbs, hippocampus, and cerebellum, where ·NO plays the important roles. In contrast, low SOD activity was observed in the axonal neurofiber bundles, although the regions contain a lot of membrane lipids, which was thought to be peroxidized by O 2·− and related radicals such as ·OH in the regions. From these findings, it was suggested that the SOD did not only play a role in protecting the neurons from endogenously formed O 2·−, but also play a role in preservation of beneficial natures of ·NO in the brain. 相似文献
19.
The reduction of ferricytochrome c by O 2− and CO 2− was studied in the pH range 6.6–9.2 and Arrhenius as well as Eyring parameters were derived from the rate constants and their temperature dependence. Ionic effects on the rate indicate that the redox process proceeds through a multiply-positively charged interaction site on cytochrome c. It is shown that the reaction with O 2− and correspondingly with O 2 of ferrocytochrome c) is by a factor of approx. 10 3 slower than warranted by factors such as redox potential. Evidence is adduced to support the view that this slowness is connected with the role of water in the interaction between O 2−/O 2 and ferri-ferrocytochrome c in the positively charged interaction site on cytochrome c in which water molecules are specifically involved in maintaining the local structure of cytochrome c and participate in the process of electron equivalent transfer. 相似文献
20.
Norathyriol, aglycone of a xanthone C-glycoside mangiferin isolated from Tripterospermum lanceolatum, concentration dependently inhibited the formylmethionyl-leucyl-phenylalanine (fMLP)-induced superoxide anion (O 2˙−) generation and O 2 consumption in rat neutrophils. In cell-free oxygen radical generating system, norathyriol inhibited the O 2˙− generation during dihydroxyfumaric acid (DHF) autoxidation and in hypoxanthine-xanthine oxidase system. fMLP-induced transient elevation of [Ca 2+] i and the formation of inositol trisphosphate (IP 3) were significantly inhibited by norathyriol (30 μM) (about 30 and 46% inhibition, respectively). Norathyriol concentration dependently suppressed the neutrophil cytosolic phospholipase C (PLC). In contrast with the marked attenuation of fMLP-induced protein tyrosine phosphorylation (about 70% inhibition at 10 μM norathyriol), norathyriol only slightly modulated the phospholipase D (PLD) activity as determined by the formation of phosphatidic acid (PA) and, in the presence of ethanol, phosphatidylethanol (PEt). Norathyriol did not modulate the intracellular cyclic AMP level. In the presence of NADPH, the phorbol 12-myristate 13-acetate (PMA)-activated particulate NADPH oxidase activity was suppressed by norathyriol in a concentration-dependent manner and the inhibition was noncompetitive with respect to NADPH. Norathyriol inhibited the iodonitrotetrazolium violet (INT) reduction in arachidonic acid (AA)-activated cell-free NADPH oxidase system at the same concentration range as those used in the suppression of PMA-activated particulate NADPH oxidase activity. Taken together, these results suggest that the scavenging ability of norathyriol contributes to the reduction of generated O 2˙−, however, the inhibition of O 2˙− generation from neutrophils by norathyriol is attributed to the blockade of PLC pathway, the attenuation of protein tyrosine phosphorylation, and to the suppression of NADPH oxidase through the interruption of electrons transport. 相似文献
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