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)

Although in vitro studies have shown that oxygen free radicals depress the sarcolemmal Ca(2+)-pump activity and thereby may cause the occurrence of intracellular Ca2+ overload for the genesis of contractile failure, the exact relationship between changes in sarcolemmal Ca(2+)-pump activity and cardiac function due to these radicals is not clear. In this study we examined the effects of oxygen radicals on sarcolemmal Ca2+ uptake and Ca(2+)-stimulated ATPase activities as well as contractile force development by employing isolated rat heart preparations. When hearts were perfused with medium containing xanthine plus xanthine oxidase, the sarcolemmal Ca(2+)-stimulated ATPase activity and ATP-dependent Ca2+ accumulation were depressed within 1 min whereas the developed contractile force, rate of contraction and rate of relaxation were increased at 1 min and decreased over 3-20 min of perfusion. The resting tension started increasing at 2 min of perfusion with xanthine plus xanthine oxidase. Catalase showed protective effects against these alterations in heart function and sarcolemmal Ca(2+)-pump activities upon perfusion with xanthine plus xanthine oxidase whereas superoxide dismutase did not exert such effects. The combination of catalase and superoxide dismutase did not produce greater effects in comparison to catalase alone. These results are consistent with the view that the depression of heart sarcolemmal Ca2+ pump activities may result in myocardial dysfunction due to the formation of hydrogen peroxide and/or hydroxyl radicals upon perfusing the hearts with xanthine plus xanthine oxidase.
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PMID:Relationship between mechanical dysfunction and depression of sarcolemmal Ca(2+)-pump activity in hearts perfused with oxygen free radicals. 890 72

The purpose of this study was to determine the acute effects of doxorubicin and its less cardiotoxic epimer, 4'-epirubicin, on the contractile response of isolated myocytes, and to assess similarities or differences with respect to active oxygen-derived mechanisms. Calcium-tolerant myocytes from rat ventricle were field stimulated at 1.0 Hz, and the maximum extent of cell shortening, peak shortening velocity, and peak relaxation velocity of single twitches were measured by video edge detection. The contractile responses of the myocytes to the two anthracyclines were approximately equal. Exposure of the cells to 10 microM of either anthracycline for 20 min decreased all indices of contractility by 28% (p < 0.05). The active oxygen scavengers, superoxide dismutase and catalase, distinguished the extent to which active oxygen was involved in modifying cellular contractility. Paradoxically, superoxide dismutase alone (10 U/mL) decreased contractility by 21%. Nevertheless, superoxide dismutase (10 U/mL) prevented the decreases in contractility produced by doxorubicin. In contrast, superoxide dismutase only mildly (32%) protected against 4'-epirubicin. Catalase (10 U/mL), however, provided substantial (82-93%) protection against both anthracyclines. Hydrogen peroxide therefore, and presumably hydroxyl radicals, were involved in mediating the decreases in contractility from both doxorubicin and 4'-epirubicin. These results show that an acute exposure to clinically relevant concentrations of these anthracyclines significantly depresses myocyte contractility and that, in this respect, 4'-epirubicin is as potentially cardiotoxic as doxorubicin. The results with antioxidant enzymes also strongly support a free radical mechanism for the toxicity of doxorubicin and 4'-epirubicin to cardiomyocytes.
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PMID:Effects of doxorubicin, 4'-epirubicin, and antioxidant enzymes on the contractility of isolated cardiomyocytes. 896 Mar 79

This study was undertaken to examine if modulations of intracellular and extracellular Ca2+ affect the lethal cell injury and impairment of membrane transport function induced by oxidants in rabbit renal cortical slices. The oxidant t-butylhydroperoxide (t-BHP) and H2O2 increased lactate dehydrogenase (LDH) release and inhibited PAH uptake in a dose-dependent manner, but the potency of H2O2 was 100 times lower than that of t-BHP. Catalase prevented the effect of H2O2 but not that of t-BHP, suggesting that lower potency of H2O2 is attributed to the endogenous catalase activity. t-BHP induced lipid peroxidation and inhibited microsomal (Na+)-(K+)-ATPase activity. Omission of Ca2+ from the medium or addition of Ca2+ channel blockers (verapamil, diltiazem, and nifedipine) prevented the oxidant-induced LDH release. Similar effect was observed by addition of La3+. Buffering intracellular Ca2+ with BAPTA/AM decreased the oxidant-induced LDH release. However, the oxidant-induced impairment in PAH uptake was not altered under the same conditions. Also, the inhibition of microsomal (Na+)-(K+)-ATPase activity by t-BHP was not affected by verapamil, La3+, and BAPTA/AM. Dithiothreitol and glutathione prevented the oxidant-induced LDH release and reduction of PAH uptake and impeded the oxidant-induced inhibition of (Na+)-(K+)-ATPase activity and lipid peroxidation. Effects of t-BHP on TEA uptake were similar to those on PAH uptake. Modulations of intracellular or extracellular Ca2+ had little effect on the oxidant-induced lipid peroxidation. Glycine did not exert protective effect against the oxidant-induced cell injury. These results suggest strongly that Ca2+ plays an important role in the oxidant-induced LDH release but not in the oxidant-induced alterations of membrane transport function in rabbit renal cortical slices. The role of Ca2+ in oxidant-induced LDH release is not apparently associated with peroxidation of membrane lipid.
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PMID:Differential effect of Ca2+ on oxidant-induced lethal cell injury and alterations of membrane functional integrity in renal cortical slices. 897 86

The purpose of this study was to gain direct insights into mechanisms by which myoglobin induces proximal tubular cell death. To avoid confounding systemic and hemodynamic influences, an in vitro model of myoglobin cytotoxicity was employed. Human proximal tubular (HK-2) cells were incubated with 10 mg/ml myoglobin, and after 24 hours the lethal cell injury was assessed (vital dye uptake; LDH release). The roles played by heme oxygenase (HO), cytochrome p450, free iron, intracellular Ca2+, nitric oxide, H2O2, hydroxyl radical (-OH), and mitochondrial electron transport were assessed. HO inhibition (Sn protoporphyrin) conferred almost complete protection against myoglobin cytotoxicity (92% vs. 22% cell viability). This benefit was fully reproduced by iron chelation therapy (deferoxamine). Conversely, divergent cytochrome p450 inhibitors (cimetidine, aminobenzotriazole, troleandomycin) were without effect Catalase induced dose dependent cytoprotection, virtually complete, at a 5000 U/ml dose. Conversely, -OH scavengers (benzoate, DMTU, mannitol), xanthine oxidase inhibition (oxypurinol), superoxide dismutase, and manipulators of nitric oxide expression (L-NAME, L-arginine) were without effect. Intracellular (but not extracellular) calcium chelation (BAPTA-AM) caused approximately 50% reductions in myoglobin-induced cell death. The ability of Ca2+ (plus iron) to drive H2O2 production (phenol red assay) suggests one potential mechanism. Blockade of site 2 (antimycin) and site 3 (azide), but not site 1 (rotenone), mitochondrial electron transport significantly reduced myoglobin cytotoxicity. Inhibition of Na, K-ATPase driven respiration (ouabain) produced a similar protective effect. We conclude that: (1) HO-generated iron release initiates myoglobin toxicity in HK-2 cells; (2) myoglobin, rather than cytochrome p450, appears to be the more likely source of toxic iron release; (3) H2O2 generation, perhaps facilitated by intracellular Ca2+/iron, appears to play a critical role; and (4) cellular respiration/terminal mitochondrial electron transport ultimately helps mediate myoglobin's cytotoxic effect. Formation of poorly characterized toxic iron/H2O2-based reactive intermediates at this site seems likely to be involved.
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PMID:Myoglobin toxicity in proximal human kidney cells: roles of Fe, Ca2+, H2O2, and terminal mitochondrial electron transport. 906 5

Reactive oxygen species (ROS) significantly alter cell function. We examined the effects of hydrogen peroxide (H2O2) and xanthine/xanthine oxidase (X/XO) on isolated intestinal muscle cells. We assessed cell viability with the exclusion dye trypan blue and assayed the effects of H2O2 and X/XO on the intracellular redox state with the fluorescent probe 2',7'-dichlorofluorescein. Intracellular calcium concentration was measured in cells loaded with fura 2-acetoxymethyl ester, and we recorded whole membrane currents with conventional patch-clamp methods. Cells remained viable after a 5-min exposure to H2O2 and X/XO. H2O2 and X/XO led to a significant rise of the intracellular concentration of ROS. H2O2 (270 microM to 2.7 mM) as well as X/XO (0.25-16 mU; 0.5 mM xanthine) significantly increased intracellular calcium concentrations. Depletion of intracellular calcium with ryanodine or thapsigargin did not abolish the effect of ROS on the intracellular calcium concentration. In the absence of external calcium or in the presence of the calcium channel blocker nifedipine, H2O2 and X/XO still increased the intracellular calcium level. Thus calcium influx and calcium release from internal stores contributed to this rise in cytosolic calcium. Catalase and superoxide dismutase blunted or completely abolished the changes in calcium concentration elicited by H2O2 and X/XO. Exposure to ROS resulted in a rapid decline of the membrane resistance without significant changes in voltage-sensitive ion currents. We conclude that ROS disrupt the calcium homeostasis of cells at concentrations that do not lead to immediate cell death. The resulting elevation in cytosolic free calcium will activate a variety of biochemical reactions and may thus contribute to the cytotoxicity of reactive oxygen molecules.
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PMID:Reactive oxygen species and calcium homeostasis in cultured human intestinal smooth muscle cells. 922 80

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

The effect of the herbicide 4,6-dinitro-o-cresol (DNOC), a structural analogue of the classical protonophore 2,4-dinitrophenol, on the bioenergetics and inner membrane permeability of isolated rat liver mitochondria was studied. We observed that DNOC (10-50 microM) acts as a classical uncoupler of oxidative phosphorylation in rat liver mitochondria, promoting both an increase in succinate-supported mitochondrial respiration in the presence or absence of ADP and a decrease in transmembrane potential. The protonophoric activity of DNOC was evidenced by the induction of mitochondrial swelling in hyposmotic K(+)-acetate medium, in the presence of valinomycin. At higher concentrations (> 50 microM), DNOC also induces an inhibition of succinate-supported respiration, and a decrease in the activity of the succinate dehydrogenase can be observed. The addition of uncoupling concentrations of DNOC to Ca(2+)-loaded mitochondria treated with Ruthenium Red results in non-specific membrane permeabilization, as evidenced by mitochondrial swelling in isosmotic sucrose medium. Cyclosporin A, which inhibits mitochondrial permeability transition, prevented DNOC-induced mitochondrial swelling in the presence of Ca2+, which was accompanied by a decrease in mitochondrial membrane protein thiol content, owing to protein thiol oxidation. Catalase partially inhibits mitochondrial swelling and protein thiol oxidation, indicating the participation of mitochondrial-generated reactive oxygen species in this process. It is concluded that DNOC is a potent potent protonophore acting as a classical uncoupler of oxidative phosphorylation in rat liver mitochondria by dissipating the proton electrochemical gradient. Treatment of Ca(2+)-loaded mitochondria with uncoupling concentrations of DNOC results in mitochondrial permeability transition, associated with membrane protein thiol oxidation by reactive oxygen species.
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PMID:4,6-Dinitro-o-cresol uncouples oxidative phosphorylation and induces membrane permeability transition in rat liver mitochondria. 937 80

In this study, we investigated whether (1) collagen-induced platelet aggregation is associated with a burst of H2O2, (2) this oxidant species is involved in the activation of platelets, and (3) the pathways of platelet activation are stimulated by H2O2. Collagen-induced platelet aggregation was associated with production of H2O2, which was abolished by catalase, an enzyme that destroys H2O2. H2O2 production was not observed when ADP or thrombin were used as agonists. Catalase inhibited dose-dependently thromboxane A2 production, release of arachidonic acid from platelet membrane, and Inositol 1,4,5P3 (IP3) formation. In aspirin-treated platelets stimulated with high concentrations of collagen, catalase inhibited platelet aggregation, calcium mobilization, and IP3 production. This study suggests that collagen-induced platelet aggregation is associated with a burst of H2O2 that acts as a second messenger by stimulating the arachidonic acid metabolism and phospholipase C pathway.
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PMID:Hydrogen peroxide is involved in collagen-induced platelet activation. 942 1

Agaricus bisporus, Fusarium graminearum, Phycomyces blakesleeanus, unbleached and bleached, Rhizomucor miehei, and Rhizopus oryzae were examined as sources of fungal chitin/chitosan. The nitrogen content of the alkalitreated mycelia/sporangiophores obtained after optimization of culture conditions, and of similarly treated A. bisporus stipes, was 2.87, 1.29, 6.27, 6.50, 4.80, and 4.95% w/w, respectively, which relates to an estimated chitin content of 42, 19, 91, 94, 70, and 72%, respectively. The hydrogen peroxide (H2O2)-generating ability of the treated fungal materials after 8 h at pH 7.4 and 37 degrees C decreased in the order R. oryzae > P. blakesleeanus unbleached approximately R. miehi > F. graminearum > A. bisporus > P. blakesleeanus bleached. This did not correlate with estimated chitin content. The effect of these fungal materials on the rate of proliferation of murine L929 fibroblasts in culture also was examined. Both pro- and antiproliferant effects were observed. Significant (P < .05) proproliferant effects were observed on day 6 with R. miehei, R. oryzae, and P. blakesleeanus (unbleached and bleached) at 0.01% w/v. The greatest antiproliferant effect was observed with R. oryzae at 0.05% w/v on day 6 (-63% relative to the control, P < .05; cell viability, 95%). In contrast, A. bisporus failed to affect cell yield significantly at either 0.01 or 0.05% w/v. Addition of catalase to cultures containing R. oryzae or R. miehei at 0.05% w/v failed to abolish the antiproliferant effect on day 3, instead producing a small but significant (P < .05) increase in the effect. Catalase also failed to affect significantly the antiproliferant effect of F. graminearum at 0.05% w/v, but did abolish the proproliferant effect of P. blakesleeanus (unbleached and bleached) on day 3. Overall, our results suggest that the H2O2 being generated by the fungal materials modulates cell proliferation but that this effect is superimposed upon a H2O2-independent antiproliferant effect manifesting itself at the higher concentrations of fungal material. The antiproliferant effect was not attributable to Ca2+, Mg2+, or Fe2+ depletion although chelation of Fe2+ did correlate with H2O2-generating ability. Only P. blakesleeanus appears to lack this antiproliferant activity while retaining H2O2-generating activity. These results may aid the selection of fungal chitin/chitosan for further evaluation as a potential wound management material.
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PMID:Biocompatibility of potential wound management products: hydrogen peroxide generation by fungal chitin/chitosans and their effects on the proliferation of murine L929 fibroblasts in culture. 945 61

Ca(2+)-loaded rat liver mitochondria treated with 3,5,3'-triiodothyronine (T3) undergo nonspecific inner membrane permeabilization, as evidenced by mitochondrial swelling, a decrease in membrane potential (delta psi), and an increase in the rate of oxygen uptake. T3 analogues thyroxine (T4), 3',5'-diiodothyronine (T2), and 3,5',3'-triiodothyronine (reverse T3), in decreasing order of potency, resulted in a similar but less extensive effect. Permeabilization induced by T3 is dependent on Ca2+ (1 microM) and T3 (0.5-25 microM) concentrations and is inhibited by cyclosporin A, a known inhibitor of mitochondrial permeability transition. Catalase or dithiothreitol also prevents membrane permeabilization, suggesting the participation of membrane protein thiol group oxidation induced by reactive oxygen species. The determination of the mitochondrial membrane protein thiol group content after treatment with Ca2+ and T3 shows a significant decrease, due to thiol oxidation. When mitochondria are incubated in the presence of inorganic phosphate and the protonophore carbonyl cyanide p-trifluoromethoxyphenylhydrazone, mitochondrial swelling still occurs after treatment with T3 and high Ca2+ concentrations, suggesting that mitochondrial permeabilization is not dependent on T3-induced delta psi or matrix pH alterations. Under these experimental conditions, when no oxygen is present in the incubation medium, no permeabilization occurs, suggesting that the permeabilization is dependent on mitochondrial-generated reactive oxygen species. Confirming this hypothesis, superoxide generation in a suspension of submitochondrial particles is increased when T3 is present. Our results lead to the conclusion that T3 induces a situation of oxidative stress in isolated liver mitochondria, with Ca(2+)-mediated membrane protein thiol oxidation and nonspecific inner membrane permeabilization.
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PMID:3,5,3'-triiodothyronine induces mitochondrial permeability transition mediated by reactive oxygen species and membrane protein thiol oxidation. 963 10


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