Showing papers on "Catalase published in 2004"

Reactive Oxygen Species, Aging, and Antioxidative Nutraceuticals.

Abstract: The important roles of reactive oxygen species in diseases related to aging and the necessity and benefits of antioxidative nutraceuticals in the prevention of diseases and promotion of healthy aging have been extensively reported in recent years Oxygen is an essential component of living organisms The generation of reactive oxygen species such as superoxide anion, hydrogen peroxide, hydroxyl radicals, and singlet oxygen is inevitable in aerobic metabolism of the body Reactive oxygen species cause lipid oxidation, protein oxidation, DNA strand break and base modification, and modulation of gene expression In the past several years, unprecedented progress has been made in the recognition and understanding of roles of reactive oxygen species in many diseases These include atherosclerosis, vasospasms, cancers, trauma, stroke, asthma, hyperoxia, arthritis, heart attack, age pigments, dermatitis, cataractogenesis, retinal damage, hepatitis, liver injury, and periodontis, which are age-related The body protects itself from the potential damages of reactive oxygen species Its first line of defense is superoxide dismutases, glutathione peroxidases, and catalase Scientists have indicated that antioxidant nutraceuticals supplied from daily diets quench the reactive oxygen species or are required as cofactors for antioxidant enzymes Nutraceuticals play significant roles in the prevention of a number of age-related diseases and are essential for healthy aging Epidemiological studies also reported the relevance of antioxidative nutraceuticals to health issues and the prevention of age-related diseases Health-conscious consumers have made antioxidative nutraceuticals the leading trend in the food industry worldwide in recent years

Salinity up‐regulates the antioxidative system in root mitochondria and peroxisomes of the wild salt‐tolerant tomato species Lycopersicon pennellii

Abstract: The effect of salinity on the antioxidative system of root mitochondria and peroxisomes of a cultivated tomato Lycopersicon esculentum (Lem) and its wild salt-tolerant related species L. pennellii (Lpa) was studied. Salt stress induced oxidative stress in Lem mitochondria, as indicated by the increased levels of lipid peroxidation and H(2)O(2). These changes were associated with decreased activities of superoxide dismutase (SOD) and guaiacol peroxidases (POD) and contents of ascorbate (ASC) and glutathione (GSH). By contrast, in mitochondria of salt-treated Lpa plants both H(2)O(2) and lipid peroxidation levels decreased while the levels of ASC and GSH and activities of SOD, several isoforms of ascorbate peroxidase (APX), and POD increased. Similarly to mitochondria, peroxisomes isolated from roots of salt-treated Lpa plants exhibited also decreased levels of lipid peroxidation and H(2)O(2) and increased SOD, ascorbate peroxidase (APX), and catalase (CAT) activities. In spite of the fact that salt stress decreased activities of antioxidant enzymes in Lem peroxisome, oxidative stress was not evident in these organelles.

p53-induced up-regulation of MnSOD and GPx but not catalase increases oxidative stress and apoptosis.

Abstract: p53-mediated apoptosis may involve the induction of redox-controlling genes, resulting in the production of reactive oxygen species. Microarray expression analysis of doxorubicin exposed, related human lymphoblasts, p53 wild-type (WT) Tk6, and p53 mutant WTK1 identified the p53-dependent up-regulation of manganese superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx). Consensus p53 binding sequences were identified in human MnSOD and GPx promoter regions. A 3-fold increase in the MnSOD promoter activity was observed after the induction of p53 in Li-Fraumeni syndrome (LFS) fibroblast, TR9-7, expressing p53 under the control of a tetracycline-regulated promoter. An increased protein expression of endogenous MnSOD and GPx also positively correlated with the level of p53 induction in TR9-7 cells. However, catalase (CAT) protein expression remained unaltered after p53 induction. We also examined the expression of MnSOD, GPx, and CAT in a panel of normal or LFS fibroblasts, containing either WT or mutant p53. We found increased MnSOD enzymatic activity, MnSOD mRNA expression, and MnSOD and GPx protein in LFS fibroblasts carrying a WT p53 allele when compared with homozygous mutant p53 isogenic cells. The CAT protein level was unchanged in these cells. We observed both the release of cytochrome C and Ca(2+) from the mitochondria into the cytoplasm and an increased frequency of apoptotic cells after p53 induction in the TR9-7 cells that coincided with an increased expression of MnSOD and GPx, and the level of reactive oxygen species. The increase in apoptosis was reduced by the antioxidant N-acetylcysteine. These results identify a novel mechanism of p53-dependent apoptosis in which p53-mediated up-regulation of MnSOD and GPx, but not CAT, produces an imbalance in antioxidant enzymes and oxidative stress.

Intrinsic oxidative stress in cancer cells: a biochemical basis for therapeutic selectivity

Abstract: Therapeutic selectivity is one of the most important considerations in cancer chemotherapy. The design of therapeutic strategies to preferentially kill malignant cells while minimizing harmful effects to normal cells depends on our understanding of the biological differences between cancer and normal cells. We have previously demonstrated that certain agents generating reactive oxygen species (ROS) such as 2-methoxyestradiol (2-ME) preferentially kill human leukemia cells without exhibiting significant cytotoxicity in normal lymphocytes. The purpose of the current study was to investigate the biochemical basis for such selective anticancer activity. Flow cytometric analyses were utilized to measure intracellular O2 − levels and apoptosis. MTT assays were used as indicators of cellular viability. Western blot analysis was used to measure the expression of antioxidant enzymes in cancer and normal cells. Malignant cells in general are more active than normal cells in the production of O2 −, are under intrinsic oxidative stress, and thus are more vulnerable to damage by ROS-generating agents. The intrinsic oxidative stress in cancer cells was associated with the upregulation of SOD and catalase protein expression, likely as a mechanism to tolerate increased ROS stress. The increase in SOD and catalase expression was observed both in primary human leukemia cells and in primary ovarian cancer cells. Both malignant cell types were more sensitive to 2-ME than their normal counterparts, as demonstrated by the significant accumulation of O2 − and subsequent apoptosis. The administration of ROS scavengers in combination with 2-ME prevented the accumulation of O2 − and abrogated apoptosis induction. O2 − is an important mediator of 2-ME-induced apoptosis. The increased oxidative stress in cancer cells forces these cells to rely more on antioxidant enzymes such as SOD for O2 − elimination, thus making the malignant cells more vulnerable to SOD inhibition than normal cells.

Modulation of Oxidant and Antioxidant Enzyme Expression and Function in Vascular Cells

Abstract: Pathological conditions that predispose to cardiovascular events, such as hypertension, hypercholesterolemia, and diabetes, are associated with oxidative stress. These observations and further data derived from a plethora of investigations provided accumulating evidence that oxidative stress is decisively involved in the pathogenesis of endothelial dysfunction and atherosclerosis. Several enzymes expressed in vascular tissue contribute to production and efficient degradation of reactive oxygen species, and enhanced activity of oxidant enzymes and/or reduced activity of antioxidant enzymes may cause oxidative stress. Various agonists, pathological conditions, and therapeutic interventions lead to modulated expression and function of oxidant and antioxidant enzymes, including NAD(P)H oxidase, endothelial nitric oxide synthase, xanthine oxidase, myeloperoxidase, superoxide dismutases, catalase, thioredoxin reductase, and glutathione peroxidase. Data from numerous studies underline the importance of dysregulated oxidant and antioxidant enzymes for the development and progression of atherosclerotic disease in animal models and humans. Specific pharmacological modulation of key enzymes involved in the propagation of oxidative stress rather than using direct antioxidants may be an approach to reduce oxygen radical load in the vasculature and subsequent disease progression in humans. This review focuses on the modulation of expression and activity of major antioxidant and oxidant enzymes expressed in vascular cells.

Catalase deficiency drastically affects gene expression induced by high light in Arabidopsis thaliana.

Abstract: In plants, hydrogen peroxide (H 2 O 2 ) plays a major signaling role in triggering both a defense response and cell death. Increased cellular H 2 O 2 levels and subsequent redox imbalances are managed at the production and scavenging levels. Because catalases are the major H 2 O 2 scavengers that remove the bulk of cellular H 2 O 2 , altering their levels allows in planta modulation of H 2 O 2 concentrations. Reduced peroxisomal catalase activity increased sensitivity toward both ozone and photorespiratory H 2 O 2 -induced cell death in transgenic catalase-deficient Arabidopsis thaliana. These plants were used as a model system to build a comprehensive inventory of transcriptomic variations, which were triggered by photorespiratory H 2 O 2 induced by high-light (HL) irradiance. In addition to an H 2 O 2 -dependent and -independent type of transcriptional response during light stress, microarray analysis on both control and transgenic catalase-deficient plants, exposed to 0, 3, 8, and 23 h of HL, revealed several specific regulatory patterns of gene expression. Thus, photorespiratory H 2 O 2 has a direct impact on transcriptional programs in plants.

Antioxidant enzyme responses to NaCl stress in Cassia angustifolia

Abstract: Seeds of Cassia angustifolia Vahl. were subjected to 0, 20, 50, 100 mM NaCl for 7 d in order to study the effect of salt stress on growth parameters, endogenous Na+ and Cl− concentrations, antioxidant system, lipid peroxidation, hydrogen peroxide, and proline contents. Salinity affected all of the considered parameters and caused a great reduction in plant biomass. The root and shoot length, fresh and dry mass and germination percentage were inhibited by NaCl treatments. These changes were associated with an increase in the Na+ and Cl− contents in the seedlings and increased activities of superoxide dismutase, catalase, peroxidase, and polyphenol oxidase. The increased enzyme activity coincided with decreased ascorbate content and enhanced H2O2 and proline content.

Hydrogen Peroxide Poisoning

Abstract: Hydrogen peroxide is an oxidising agent that is used in a number of household products, including general-purpose disinfectants, chlorine-free bleaches, fabric stain removers, contact lens disinfectants and hair dyes, and it is a component of some tooth whitening products. In industry, the principal use of hydrogen peroxide is as a bleaching agent in the manufacture of paper and pulp. Hydrogen peroxide has been employed medicinally for wound irrigation and for the sterilisation of ophthalmic and endoscopic instruments. Hydrogen peroxide causes toxicity via three main mechanisms: corrosive damage, oxygen gas formation and lipid peroxidation. Concentrated hydrogen peroxide is caustic and exposure may result in local tissue damage. Ingestion of concentrated (>35%) hydrogen peroxide can also result in the generation of substantial volumes of oxygen. Where the amount of oxygen evolved exceeds its maximum solubility in blood, venous or arterial gas embolism may occur. The mechanism of CNS damage is thought to be arterial gas embolisation with subsequent brain infarction. Rapid generation of oxygen in closed body cavities can also cause mechanical distension and there is potential for the rupture of the hollow viscus secondary to oxygen liberation. In addition, intravascular foaming following absorption can seriously impede right ventricular output and produce complete loss of cardiac output. Hydrogen peroxide can also exert a direct cytotoxic effect via lipid peroxidation. Ingestion of hydrogen peroxide may cause irritation of the gastrointestinal tract with nausea, vomiting, haematemesis and foaming at the mouth; the foam may obstruct the respiratory tract or result in pulmonary aspiration. Painful gastric distension and belching may be caused by the liberation of large volumes of oxygen in the stomach. Blistering of the mucosae and oropharyngeal burns are common following ingestion of concentrated solutions, and laryngospasm and haemorrhagic gastritis have been reported. Sinus tachycardia, lethargy, confusion, coma, convulsions, stridor, sub-epiglottic narrowing, apnoea, cyanosis and cardiorespiratory arrest may ensue within minutes of ingestion. Oxygen gas embolism may produce multiple cerebral infarctions. Although most inhalational exposures cause little more than coughing and transient dyspnoea, inhalation of highly concentrated solutions of hydrogen peroxide can cause severe irritation and inflammation of mucous membranes, with coughing and dyspnoea. Shock, coma and convulsions may ensue and pulmonary oedema may occur up to 24-72 hours post exposure. Severe toxicity has resulted from the use of hydrogen peroxide solutions to irrigate wounds within closed body cavities or under pressure as oxygen gas embolism has resulted. Inflammation, blistering and severe skin damage may follow dermal contact. Ocular exposure to 3% solutions may cause immediate stinging, irritation, lacrimation and blurred vision, but severe injury is unlikely. Exposure to more concentrated hydrogen peroxide solutions (>10%) may result in ulceration or perforation of the cornea. Gut decontamination is not indicated following ingestion, due to the rapid decomposition of hydrogen peroxide by catalase to oxygen and water. If gastric distension is painful, a gastric tube should be passed to release gas. Early aggressive airway management is critical in patients who have ingested concentrated hydrogen peroxide, as respiratory failure and arrest appear to be the proximate cause of death. Endoscopy should be considered if there is persistent vomiting, haematemesis, significant oral burns, severe abdominal pain, dysphagia or stridor. Corticosteroids in high dosage have been recommended if laryngeal and pulmonary oedema supervene, but their value is unproven. Endotracheal intubation, or rarely, tracheostomy may be required for life-threatening laryngeal oedema. Contaminated skin should be washed with copious amounts of water. Skin lesions should be treated as thermal burns; surgery may be required for deep burns. In the case of eye exposure, the affected eye(s) shod eye(s) should be irrigated immediately and thoroughly with water or 0.9% saline for at least 10-15 minutes. Instillation of a local anaesthetic may reduce discomfort and assist more thorough decontamination.

Glutathione peroxidase-catalase cooperativity is required for resistance to hydrogen peroxide by mature rat oligodendrocytes

Abstract: Oxidative mechanisms of injury are important in many neurological disorders, including hypoxic-ischemic brain damage. Cerebral palsy after preterm birth is hypothesized to be caused by hypoxic-ischemic injury of developing oligodendrocytes (OLs). Here we examined the developmental sensitivity of OLs to exogenous hydrogen peroxide (H2O2) with stage-specific rat oligodendrocyte cultures. We found that H2O2 itself or that generated by glucose oxidase was more toxic to developing than to mature OLs. Mature OLs were able to degrade H2O2 faster than developing OLs, suggesting that higher antioxidant enzyme activity might be the basis for their resistance. Catalase expression and activity were relatively constant during oligodendrocyte maturation, whereas glutathione peroxidase (GPx) was upregulated with a twofold to threefold increase in its expression and activity. Thus, it appeared that the developmental change in resistance to H2O2 was caused by modulation of GPx but not by catalase expression. To test the relative roles of catalase and GPx in the setting of oxidative stress, we measured enzyme activity in cells exposed to H2O2 and found that H2O2 induced a decrease in catalase activity in developing but not in mature OLs. Inhibition of GPx by mercaptosuccinate led to an increase in the vulnerability of mature OLs to H2O2 as well as a reduction in catalase activity. Finally, H2O2-dependent inactivation of catalase in developing OLs was prevented by the GPx mimic ebselen. These data provide evidence for a key role for GPx-catalase cooperativity in the resistance of mature OLs to H2O2-induced cell death.

Free radicals in cell biology.

Abstract: In aerobic cells, free radicals are constantly produced mostly as reactive oxygen species Once produced, free radicals are removed by antioxidant defenses including enzyme catalase, glutathione peroxidase, and superoxide dismutase Reactive oxygen species, including nitric oxide and related species, commonly exert a series of useful physiological effects However, imbalance between prooxidant and antioxidant defenses in favor of prooxidants results in oxidative stress associated with the oxidative modification of biomolecules such as lipids, proteins, and nucleic acids Alone or in combination with primary ethiological factors, free radicals are involved in a pathogenesis of more than a hundred diseases This chapter reviews the basic science of some of the potential sources and characteristics of free radicals, as well as antioxidant enzymes Special attention is paid to the role of free radicals in the pathogenesis of atherosclerosis and immunology-mediated inflammatory reaction

Tissue-specific oxidative stress responses in fish exposed to 2,4-D and azinphosmethyl.

Abstract: Species- and tissue-specific defenses against the possibility of oxidative stress and lipid peroxidation were compared in adult fish, Oreochromis niloticus and Cyprinus carpio, exposed to 2,4-dichlorophenoxyacetic acid (2,4-D), azinphosmethyl and their combination for 96 h. Superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase activities were monitored in kidney, brain and gill. In all exposure groups there was a marked increase in SOD activity in gill tissues in both fish species, while it was at the control level in other tissues. The highest elevation of SOD activity by combined treatment was observed in C. carpio. Individual and combined treatments caused an elevation in catalase and GPx activities in kidney of C. carpio. Catalase activity was unaffected in brain of O. niloticus, while GPx activity was decreased after all treatments. Glutathione S-transferase (GST) activity was higher than the control levels in kidney of both fish exposed to pesticides. No significant changes were observed in malondialdehyde level in kidney and brain of C. carpio. Our results indicate that the toxicities of azinphosmethyl and 2,4-D may be related to oxidative stress. Also, the results show that SOD activity in gill and GST activity in kidney may be used as biomarkers for pollution monitoring and indicate that the activities of certain biomarkers in C. carpio are more sensitive to pesticides than those in O. niloticus.

Catalase protects cardiomyocyte function in models of type 1 and type 2 diabetes.

Abstract: Many diabetic patients suffer from a cardiomyopathy that cannot be explained by poor coronary perfusion. Reactive oxygen species (ROS) have been proposed to contribute to this cardiomyopathy. Consistent with this we found evidence for induction of the antioxidant genes for catalase in diabetic OVE26 hearts. To determine whether increased antioxidant protection could reduce diabetic cardiomyopathy, we assessed cardiac morphology and contractility, Ca 2+ handling, malondialdehyde (MDA)-modified proteins, and ROS levels in individual cardiomyocytes isolated from control hearts, OVE26 diabetic hearts, and diabetic hearts overexpressing the antioxidant protein catalase. Diabetic hearts showed damaged mitochondria and myofibrils, reduced myocyte contractility, slowed intracellular Ca 2+ decay, and increased MDA-modified proteins compared with control myocytes. Overexpressing catalase preserved normal cardiac morphology, prevented the contractile defects, and reduced MDA protein modification but did not reverse the slowed Ca 2+ decay induced by diabetes. Additionally, high glucose promoted significantly increased generation of ROS in diabetic cardiomyocytes. Chronic overexpression of catalase or acute in vitro treatment with rotenone, an inhibitor of mitochondrial complex I, or thenoyltrifluoroacetone, an inhibitor of mitochondrial complex II, eliminated excess ROS production in diabetic cardiomyocytes. The structural damage to diabetic mitochondria and the efficacy of mitochondrial inhibitors in reducing ROS suggest that mitochondria are a source of oxidative damage in diabetic cardiomyocytes. We also found that catalase overexpression protected cardiomyocyte contractility in the agouti model of type 2 diabetes. These data show that both type 1 and type 2 diabetes induce damage at the level of individual myocytes, and that this damage occurs through mechanisms utilizing ROS.

Superoxide dismutase, catalase and peroxidase activities do not confer protection against oxidative damage in salt‐stressed cowpea leaves

Abstract: Summary • The aim of this study was to determine whether guaiacol peroxidase (POX), superoxide dismutase (SOD) and catalase (CAT) activities are effective in the protection and recovery of cowpea (Vigna unguiculata (L.) Walp.) leaves exposed to a salt-induced oxidative stress. The salt treatment (200 mm NaCl) was imposed during six consecutive days and the salt withdrawal after 3 d (recovery treatment). Control plants received no NaCl treatment. • The salt treatment caused almost complete cessation of leaf relative growth rate in parallel with the transpiration rate. The restriction in leaf growth was associated with a progressive increase in membrane damage, lipid peroxidation and proline content. Salt withdrawal induced a significant recovery in both leaf growth rate and transpiration. Surprisingly, these prestressed/recovered plants showed only a slight recovery in leaf lipid peroxidation and membrane damage. • Leaf CAT activity experienced a twofold decrease only after 1 d NaCl treatment, and salt withdrawal had no effect on its recovery. SOD activity did not change compared with control plants. By contrast, POX activity significantly increased after 1 d NaCl treatment and showed a significant recovery to levels near to those of control. • In conclusion, it appears that the ability of cowpea plants to survive under high levels of salinity is not caused by an operating antioxidant system involving SOD, POX and CAT activities in mature leaves.

Role of hydrogen peroxide in bactericidal action of catechin.

Abstract: Catechin (epicatechin (EC), epicatechin gallate (ECg), epigallocatechin (EGC) and epigallocatechin gallate (EGCg)), which occur in green tea and black tea, possess strong bactericidal action. We observed a reactive oxygen species that was generated from the catechins as the active mechanism: and this reactive oxygen was identified. EGCg reacted with the dissolved oxygen in aqueous solution, resulting in the generation of hydrogen peroxide. Hydrogen peroxide production derived from EGCg rose with increasing pH. EGCg (0.22 mmol/l) in neutral solution (0.1 mol/l phosphate buffer pH 7.0: PBS) quantitatively generated 0.2 mmol/l hydrogen peroxide after 60 min incubation. The bactericidal effect of EGCg is dependent on hydrogen peroxide levels produced by EGCg; moreover, EGCg action was inhibited by treatment with catalase. Both bactericidal effects correlated closely when the effects of EGCg and hydrogen peroxide for the bacterium (9 of 10 kinds of bacterial strains) were examined. Therefore, hydrogen peroxide, which is generated by EGCg, appears to be involved in the bactericidal action of EGCg.

Generation of hydrogen peroxide primarily contributes to the induction of Fe(II)-dependent apoptosis in Jurkat cells by (−)-epigallocatechin gallate

Abstract: Although (-)-epigallocatechin gallate (EGCG) has been reported to induce apoptosis in a variety of tumor cells, detailed mechanisms remain to be explored. In the present study, we investigated the antitumor mechanism of EGCG by using human T-cell acute lymphoblastic leukemia Jurkat cells. We focused on the involvement of reactive oxygen species, as we found previously that EGCG caused apoptotic cell death in osteoclastic cells due mainly to promotion of the reduction of Fe(III) to Fe(II) to trigger Fenton reaction, which affords hydroxyl radical from hydrogen peroxide [H(2)O(2) + Fe(II) --> (*)OH + OH(-) + Fe(III)]. EGCG (12.5-50 micro M) decreased the viability of Jurkat cells and caused concomitant increase in cellular caspase-3 activity. Catalase and the Fe(II)-chelating reagent o-phenanthroline suppressed the EGCG effects, indicating involvements of both H(2)O(2) and Fe(II) in the mechanism. Unexpectedly, epicatechin gallate (ECG), which has Fe(III)-reducing potency comparable with EGCG, failed to decrease the viability of Jurkat cells, while epigallocatechin (EGC), which has low capacity to reduce Fe(III), showed cytotoxic effects similar to EGCG. These results suggest that, unlike in osteoclastic cells, a mechanism other than Fe(III) reduction plays a role in catechin-mediated Jurkat cell death. We found that EGCG causes an elevation of H(2)O(2) levels in Jurkat cell culture, in cell-free culture medium and sodium phosphate buffer. Catechins with a higher ability to produce H(2)O(2) were more cytotoxic to Jurkat cells. Hydrogen peroxide itself exerted Fe(II)-dependent cytotoxicity. Amongst tumor and normal cell lines tested, cells exhibiting lower H(2)O(2)-eliminating activity were more sensitive to EGCG. From these findings, we propose the mechanism that make catechins cytotoxic in certain tumor cells is due to their ability to produce H(2)O(2) and that the resulting increase in H(2)O(2) levels triggers Fe(II)-dependent formation of highly toxic hydroxyl radical, which in turn induces apoptotic cell death.

Photo-irradiated titanium dioxide catalyzes site specific DNA damage via generation of hydrogen peroxide.

Abstract: Titanium dioxide (TiO2) is a potential photosensitizer for photodynamic therapy. In this study, the mechanism of DNA damage catalyzed by photo-irradiated TiO2 was examined using [32P]-5'-end-labeled DNA fragments obtained from human genes. Photo-irradiated TiO2 (anatase and rutile) caused DNA cleavage frequently at the guanine residue in the presence of Cu(II) after E. coli formamidopyrimidine-DNA glycosylase treatment, and the thymine residue was also cleaved after piperidine treatment. Catalase, SOD and bathocuproine, a chelator of Cu(I), inhibited the DNA damage, suggesting the involvement of hydrogen peroxide, superoxide and Cu(I). The photocatalytic generation of Cu(I) from Cu(II) was decreased by the addition of SOD. These findings suggest that the inhibitory effect of SOD on DNA damage is due to the inhibition of the reduction of Cu(II) by superoxide. We also measured the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an indicator of oxidative DNA damage, and showed that anatase is more active than rutile. On the other hand, high concentration of anatase caused DNA damage in the absence of Cu(II). Typical free hydroxyl radical scavengers, such as ethanol, mannnitol, sodium formate and DMSO, inhibited the copper-independent DNA photodamage by anatase. In conclusion, photo-irradiated TiO2 particles catalyze the copper-mediated site-specific DNA damage via the formation of hydrogen peroxide rather than that of a free hydroxyl radical. This DNA-damaging mechanism may participate in the phototoxicity of TiO2.

Retardation of Atherosclerosis by Overexpression of Catalase or Both Cu/Zn-Superoxide Dismutase and Catalase in Mice Lacking Apolipoprotein E

Abstract: Oxidative stress has been suggested to potentiate atherogenesis. However, studies that have investigated the effect of antioxidants on atherosclerosis showed inconsistent results, ie, atherosclerosis was either retarded or not changed by dietary antioxidants. This report directly examined the effect of overexpressing Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and/or catalase on atherosclerosis and lipid peroxidation in mice lacking apolipoprotein E (ApoE / ). Based on lipid staining of the en face of the aorta tree and the serial sections of the proximal aorta, ApoE / mice overexpressing catalase or both Cu/Zn-SOD and catalase had smaller and relatively early stages of atherosclerotic lesions (eg, foam cells and free lipids) when compared with ApoE / mice, who developed more advanced lesions (eg, fibrous caps and acellular areas). In addition, the retarded development of atherosclerosis was correlated with a reduced F2-isoprostanes in the plasma and aortas in ApoE / mice overexpressing catalase or both Cu/Zn-SOD and catalase. In contrast, the levels of F2-isoprostanes and atherosclerosis in the ApoE / mice overexpressing Cu/Zn-SOD alone were comparable to ApoE / control mice. These observations implied that endogenously produced hydrogen peroxide, but not superoxide anions, contributed to the formation of oxidized lipids and the development of atherosclerosis in ApoE / mice. (Circ Res. 2004;95:1075-1081.)

Role of reactive oxygen species in LPS-induced production of prostaglandin E2 in microglia.

Abstract: We determined the roles of reactive oxygen species (ROS) in the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin E2 (PGE2) in lipopolysaccharide (LPS)-activated microglia. LPS treatment increased intracellular ROS in rat microglia dose-dependently. Pre-treatment with superoxide dismutase (SOD)/catalase, or SOD/catalase mimetics that can scavenge intracellular ROS, significantly attenuated LPS-induced release in PGE2. Diphenylene iodonium (DPI), a non-specific NADPH oxidase inhibitor, decreased LPS-induced PGE2 production. In addition, microglia from NADPH oxidase-deficient mice produced less PGE2 than those from wild-type mice following LPS treatment. Furthermore, LPS-stimulated expression of COX-2 (determined by RT-PCR analysis of COX-2 mRNA and western blot for its protein) was significantly reduced by pre-treatment with SOD/catalase or SOD/catalase mimetics. SOD/catalase mimetics were more potent than SOD/catalase in reducing COX-2 expression and PGE2 production. As a comparison, scavenging ROS had no effect on LPS-induced nitric oxide production in microglia. These results suggest that ROS play a regulatory role in the expression of COX-2 and the subsequent production of PGE2 during the activation process of microglia. Thus, inhibiting NADPH oxidase activity and subsequent ROS generation in microglia can reduce COX-2 expression and PGE2 production. These findings suggest a potential therapeutic intervention strategy for the treatment of inflammation-mediated neurodegenerative diseases.