Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of antioxidants, reactive oxygen species (ROS) scavengers, and Ca2+ on cisplatin-induced renal cell injury were studied in rabbit renal cortical slices in vitro. Cisplatin induced LDH release and lipid peroxidation, inhibition of PAH uptake, and GSH depletion. These changes were significantly prevented by thiols (DTT and GSH), antioxidants (DPPD and BHA), and an iron chelator (deferoxamine). Superoxide dismutase partially reduced the cisplatin-induced LDH release without affecting the lipid peroxidation and the GSH depletion. Catalase did not affect the LDH release and the lipid peroxidation induced by cisplatin. Hydroxyl radical scavengers prevented the lipid peroxidation, whereas they did not alter the LDH release, the inhibition of PAH uptake, and the GSH depletion induced by cisplatin. Removal of Ca2+ or addition of EGTA to the incubation medium did not alter cisplatin effects on LDH release and lipid peroxidation. Buffering intracellular Ca2+ with quin-2/AM or inhibition of intracellular Ca2+ release with TMB-8 significantly reduced the cisplatin effect on LDH release without any effect on the lipid peroxidation and the GSH depletion. Ruthenium red attenuated the LDH release, the lipid peroxidation, and the inhibition of PAH uptake mediated by cisplatin. La3+ prevented the cisplatin effect on the LDH release, whereas it did not affect the lipid peroxidation, the inhibition of PAH uptake, and the GSH depletion by cisplatin. These results suggest that cisplatin induces a lethal cell injury by lipid peroxidation-dependent and -independent mechanisms and that the cell injury and the lipid peroxidation by cisplatin are iron-dependent. In addition, the data indicate that the Ca2+ released from intracellular stores, but not the Ca2+ moved from extracellular space, plays a role in the cisplatin-induced cell injury independent of lipid peroxidation.
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PMID:Effects of antioxidants and Ca2+ in cisplatin-induced cell injury in rabbit renal cortical slices. 934 94

We have previously demonstrated that each region of the ultraviolet (UV) spectrum (UVA, UVB, and UVC) induces the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) in purified calf thymus DNA and HeLa cells in a fluence-dependent manner. In the present study, we further characterize the possible reactive oxygen species (ROS) that are involved in the induction of 8-oxodGuo by UV radiation. Sodium azide, a singlet oxygen (1O2) scavenger though its quenching effect on HO. was also reported, inhibited 8-oxodGuo production in calf thymus DNA exposed to UVA, UVB, or UVC in a concentration-dependent fashion with maximal quenching effect of over 90% at a concentration of 10 mM. Catalase, at a concentration of 50 U/ml, reduced the yields of UVA- and UVB-induced 8-oxodGuo formation by approximately 50%, but had little effect on UVC-induced 8-oxodGuo production. In contrast, 50 U/ml of superoxide dismutase (SOD) did not affect induction of 8-oxodGuo by any portion of the UV spectrum. Hydroxyl radical (HO.) scavengers mannitol and dimethylsulfoxide (DMSO) moderately reduced the levels of 8-oxodGuo induced by UVA and UVB, but not those by UVC. Instead, mannitol and DMSO enhanced the formation of 8-oxodGuo induced by UVC. These results suggest that certain types of ROS are involved in UV-induced 8-oxodGuo formation with 1O2 playing the predominant role throughout the UV spectrum. Except for UVC, other ROS such as hydrogen peroxide (H2O2) and HO. may also be involved in UVA- and UVB-induced oxidative DNA damage. Superoxide anion appears not to participate in UV-induced oxidation of guanosine in calf thymus DNA, as SOD did not display any quenching effects.
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PMID:Identification of possible reactive oxygen species involved in ultraviolet radiation-induced oxidative DNA damage. 935 40

Previously, we have shown that aqueous cigarette tar (ACT) extracts contain a long-lived tar radical that associates with DNA in isolated rat alveolar macrophages and causes DNA damage in isolated rat thymocytes. These ACT solutions reduce oxygen to produce superoxide and, ultimately, hydrogen peroxide. In this study, we report the fractionation of ACT solutions prepared from the tar from five cigarettes using Sephadex columns. The fractions were analyzed by UV and electron paramagnetic resonance (EPR) spectroscopy and gas chromatography/mass spectrometry (GC/MS). The fractions containing polyphenolic species (principally catechol and hydroquinone, as determined by MS) caused most of the observed DNA damage in rat thymocytes. These DNA-damaging fractions produced superoxide, H2O2, and hydroxyl radicals. Stable free radicals were identified as o- and p-benzosemiquinone radicals by EPR spectroscopy. Hydroxyl radicals were detected by EPR spin-trapping with 5, 5-dimethyl-1-pyrroline N-oxide (DMPO). Catalase inhibited the EPR signal of the DMPO-OH adduct, indicating that H2O2 is the precursor of the hydroxyl radical spin adduct. The Sephadex separation resulted in a 90-fold concentration of the hydrogen peroxide-generating capacity of the fractions that contained polyphenols, relative to the unfractionated ACT solution. Another fraction, which contained nicotine, caused some DNA damage, but this damage was 28-fold less than the damage caused by the most damaging phenolic fraction. These results support our hypothesis that the tar radical system is an equilibrium mixture of semiquinones, hydroquinones, and quinones. The tar radical associates with DNA, causes DNA damage, and very likely is involved in the toxicity associated with cigarette smoking.
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PMID:Fractionation of aqueous cigarette tar extracts: fractions that contain the tar radical cause DNA damage. 958 74

Reactive oxygen species (ROS) are implicated in aging of cartilage and in the pathogenesis of osteoarthritis. However, the biological role of chondrocytes-derived ROS has not been elucidated. An in-vitro model was developed to study the role of chondrocyte-derived ROS in cartilage matrix degradation. The primary articular chondrocytes were cultured and the aggrecan matrix was radiolabeled with 35-sulfate. The labeled aggrecan matrix was washed to remove unincorporated label and chondrocytes were returned to serum free balanced salt solution. The cell-monolayer-matrix sensitivity to oxidative damage due to either hydrogen peroxide or glucose oxidase was established by monitoring the release of labeled aggrecan into the medium. Lipopolysaccharide (LPS) treatment of chondrocyte-monolayer enhanced the release of labeled aggrecan. Catalase significantly prevented the release of labeled aggrecan in LPS-chondrocyte cultures, suggesting a role for chondrocyte-derived hydrogen peroxide in aggrecan degradation. Superoxide dismutase or boiled catalase had no such inhibitory effect. The effect of several antioxidants on LPS-chondrocyte-dependent aggrecan degradation was examined. Hydroxyl radical scavengers (mannitol and thiourea) significantly decreased aggrecan degradation. A spin trapping agent N-tert-butyl-phenylnitrone (but not its inactive analog tert-butyl-phenylcarbonate) significantly decreased aggrecan degradation. Butylated hydroxytoluene also inhibited aggrecan degradation, whereas the other lipophilic antioxidant tested, propyl gallate, had a marked dose-dependent inhibitory effect. These data indicate that general antioxidants, hydroxyl radical scavengers, antioxidant vitamins, iron chelating agents, lipophilic antioxidants, and spin trapping agents can influence chondrocyte-dependent aggrecan degradation. These studies support the role of a chondrocyte-dependent oxidative mechanism in aggrecan degradation and indicate that antioxidants can prevent matrix degradation and therefore may have a preventive or therapeutic value in arthritis. The enhancement of oxidative activity in chondrocytes and its damaging effect on matrix may be an important mechanism of matrix degradation in osteoarthritis.
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PMID:Aggrecan degradation in chondrocytes is mediated by reactive oxygen species and protected by antioxidants. 1034 32

The redox cycle of 2,5-dimethoxybenzoquinone (2,5-DMBQ) is proposed as a source of reducing equivalent for the regeneration of Fe2+ and H2O2 in brown rot fungal decay of wood. Oxalate has also been proposed to be the physiological iron reductant. We characterized the effect of pH and oxalate on the 2,5-DMBQ-driven Fenton chemistry and on Fe3+ reduction and oxidation. Hydroxyl radical formation was assessed by lipid peroxidation. We found that hydroquinone (2,5-DMHQ) is very stable in the absence of iron at pH 2 to 4, the pH of degraded wood. 2,5-DMHQ readily reduces Fe3+ at a rate constant of 4.5 x 10(3) M(-1)s(-1) at pH 4.0. Fe2+ is also very stable at a low pH. H2O2 generation results from the autoxidation of the semiquinone radical and was observed only when 2,5-DMHQ was incubated with Fe3+. Consistent with this conclusion, lipid peroxidation occurred only in incubation mixtures containing both 2,5-DMHQ and Fe3+. Catalase and hydroxyl radical scavengers were effective inhibitors of lipid peroxidation, whereas superoxide dismutase caused no inhibition. At a low concentration of oxalate (50 micro M), ferric ion reduction and lipid peroxidation are enhanced. Thus, the enhancement of both ferric ion reduction and lipid peroxidation may be due to oxalate increasing the solubility of the ferric ion. Increasing the oxalate concentration such that the oxalate/ferric ion ratio favored formation of the 2:1 and 3:1 complexes resulted in inhibition of iron reduction and lipid peroxidation. Our results confirm that hydroxyl radical formation occurs via the 2,5-DMBQ redox cycle.
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PMID:Effect of pH and oxalate on hydroquinone-derived hydroxyl radical formation during brown rot wood degradation. 1453 58

The aim of this report was to answer the question how specific immunotherapy influences the antioxidant enzyme system in patients with respiratory allergy and in longer perspective to find markers suitable to assess the efficacy of treatment. In open prospective randomised study 28 patients (18 females and 10 males, age 14-48 years) with seasonal respiratory allergy were treated with allergen immunotherapy. Subjects received subcutaneous therapy with allergens absorbed on calcium phoshate or aluminium hydroxide and were analyzed by the established protocol at the beginning, after three and 12 month of the treatment. In all treatment group red cell superoxide dismutase and glutathione peroxidase activities were in the normal range in allergic patients both before and during the treatment. Catalase activity in the allergic patients was lower as compared with controls and a significant increase of the enzyme activity occurred during and at the end of the treatment. In patients treated with calcium phosphate adsorbed allergen there was a continous increase of catalase activity from beginning up to the end of observation. In the case of the aluminium hydroxide treatment there was an increase from the baseline values up in the third month of the treatment and a decrease on the 12th month. In summary, the present results open the question that allergen immunotherapy may cause imbalance of oxidants and antioxidants. To support our findings larger controlled field studies are needed.
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PMID:Monitoring antioxidant enzymes in red cells during allergen immunotherapy. 1904 84

Catalase is well known antioxidant enzyme which catalyses the dissociation of hydrogen peroxide directly into H(2)O and O(2). Mammalian catalase has been considered as 'a venerable enzyme with new mysteries'. Some aspects of its mechanism of action are mystifying and many of new findings are still unexplained. To fill up the gap we propose the 'Hydroxyl Radical Generation Theory (HRGT)' with possible mechanism. According to HRGT, mammalian catalase apart from its known catalytic reaction generates hydroxyl radicals (HRs). The HR generation mainly depends on concentration of specific substrate, hydrogen peroxide. The present theory is supported by previous experimental findings and has great deal of observational evidences. The proposed mechanism of generation of HRs answer several unexplained features of mammalian catalase, however, should be tested further.
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PMID:Hydroxyl radical generation theory: a possible explanation of unexplained actions of mammalian catalase. 2309 44


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