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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In order to determine the effects of cigarette smoke (CS) exposure on the physical properties of cells, NMR water-proton relaxation time (which measures the intracellular water organization) and ESR spin labeling (which measures membrane order) measurements were performed on cultured Jurkat T cells exposed to CS. NMR spin-lattice relaxation time (T1) decreased with CS exposure in a dose-dependent fashion. A significantly depressed T1 value was obtained even when CS was delivered through a filter. Cell viability was not affected in this condition. Superoxide dismutase (SOD) prevented the depression of T1 value. These results suggest that superoxide radicals or subsequently generated species contained in the gas phase of CS increase the intracellular water organization in viable cells. CS exposure also increased the ESR membrane order parameter of nitroxide spin label. These physical characteristic changes may be important in CS-induced cell responses and cytopathology.
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PMID:Cigarette smoke exposure increases the cell water organization and membrane order of cultured T cells. 131 43

This study was undertaken to examine the effects of oxygen free radicals on mitochondrial creatine kinase activity in rat heart. Xanthine plus xanthine oxidase (superoxide anion radical generating system) reduced mitochondrial creatine kinase activity both in a dose- and a time-dependent manner. Superoxide dismutase showed a protective effect on depression in creatine kinase activity due to xanthine plus xanthine oxidase. Hydrogen peroxide inhibited creatine kinase activity in a dose-dependent manner, this inhibition was protected by the addition of catalase. In order to understand the detailed mechanisms by which oxygen free radicals inhibit mitochondrial creatine kinase activity, the effects of oxygen free radicals on mitochondrial sulfhydryl groups were examined. Mitochondrial sulfhydryl groups contents were decreased by xanthine plus xanthine oxidase or hydrogen peroxide; this depression in sulfhydryl groups contents was prevented by the addition of superoxide dismutase or catalase. N-Ethylmaleimide (sulfhydryl group reagent) expressed inhibitory effects on the creatine kinase activity both in a dose- and a time-dependent manner; dithiothreitol or cysteine (sulfhydryl group reductant) showed protective effects on the creatine kinase activity depression induced by N-ethylmaleimide. Dithiothreitol or cysteine also blocked the depression of mitochondrial creatine kinase activity caused by xanthine plus xanthine oxidase or hydrogen peroxide. These results lead us to conclude that oxygen free radicals may inhibit mitochondrial creatine kinase activity by modifying sulfhydryl groups in the enzyme protein.
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PMID:Decrease in heart mitochondrial creatine kinase activity due to oxygen free radicals. 132 80

1. The effects of bradykinin (BK) in the microcirculation of the isolated perfused heart of the rat were examined. The kinin receptors mediating the effects of BK were characterized and the role of endothelium-derived relaxation factor (EDRF) and prostacyclin investigated. 2. The dose-related vasodilator responses elicited by bolus doses of BK (0.001-10.0 nmol) were competitively blocked by the selective kinin B2 receptor antagonist [D-Arg0,Hyp3, Thi5.8,D-Phe7]-bradykinin (pA2 = 6.8). Des-Arg9-bradykinin, a selective kinin B1 receptor agonist had no vasodilator activity at doses of up to 10 nmol. 3. L-NG-nitro arginine (100 microM; L-NOArg), an inhibitor of endothelium-dependent vasodilatation, reduced the duration but not the magnitude of the BK vasodilator response. This action of L-NOArg was not reversed by L-arginine (100 microM). 4. Superoxide dismutase (10 units ml-1), haemoglobin (10 microM) and methylene blue (MB; 1 microM), all known to modify EDRF-mediated responses, failed to alter the vasodilator action of BK. 5. Gossypol (1-15 microM), a presumed inhibitor of EDRF biosynthesis, caused a marked drop in perfusion pressure followed by vasoconstriction. These changes in coronary tone were accompanied by an irreversible depression of cardiac contractility and heart rate. Over the same concentration range gossypol abolished the vasodilator action of BK (1.0 nmol), however it also blocked the endothelium-independent vasodilator response to sodium nitroprusside (30 nmol) and the vasoconstrictor effect of endothelin-1 (10 pmol) which suggests non-specific toxic actions of gossypol. 6. Bolus injections of BK (0.001-1.Onmol) failed to elevate basal levels of prostacyclin (PGI2) as shown by assaying for its stable metabolite 6-keto-PGF<,,. In addition, BK-induced vasodilatation was not blocked by flurbiprofen (2 microM) or BW755C (7.5 microM) which are inhibitors of the arachidonic acid pathway. When added with L-NOArg (100 microM), flurbiprofe(10 microM) did not potentiate the inhibitory action of L-NOArg on the BK response. 7. These results show that the vasodilator action of BK in the rat heart is dependent on the activation of the kinin B2 receptors but independent of PGI2 release. Although a conclusive role for EDRF could not be established, this study has questioned the suitability of several agents commonly used as inhibitors of EDRF-mediated responses.
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PMID:Effects of bradykinin in the rat isolated perfused heart: role of kinin receptors and endothelium-derived relaxing factor. 165 68

Reperfusion after reversible ischemia has been shown to result in prolonged depression of contractile function ("myocardial stunning"). Recent studies suggest that oxygen free radicals may mediate postischemic dysfunction. Since heart sarcolemmal membranes, which contain several types of enzymes, ion channels and receptors play important roles to maintain cell functions, the present study was undertaken to examine the effects of oxygen free radicals on heart sarcolemmal membrane functions in vitro. In the presence of a superoxide anion radical-generating system (2mM xanthine plus 0.03 U/ml xanthine oxidase), sarcolemmal Ca(2+)-stimulated ATPase activity and ATP-dependent Ca2+ accumulation were inhibited in an incubating time-dependent manner. Both lipid peroxidation (r = 0.82) and sulfhydryl group content (r = 0.95) showed significant correlations with Ca(2+)-stimulated ATPase activity. ATP-independent Ca2+ bindings were increased upon treating the membranes with xanthine plus xanthine oxidase. Voltage-dependent Ca(2+)-channels were also affected by oxygen free radicals. The maximal number of binding sites (Bmax) for [3H]-nitrendipine binding was depressed without any changes in dissociation constant (Kd). The effects of oxygen free radicals on adrenergic receptors were more complex. Bmax for [3H]-dihydroalprenolol (DHA) binding (beta-receptor) was increased whereas Bmax for [3H]-prazosin binding [alpha 1-receptor) was decreased after incubating the membrane with xanthine plus xanthine oxidase. Kd for [3H]-DHA or [3H]-prazosin binding was increased. Superoxide dismutase showed protective effects on the changes in these membrane functions due to xanthine plus xanthine oxidase. It is suggested that oxygen free radicals damage heart sarcolemmal membrane functions which may lead to cardiac dysfunction in the stunned myocardium.
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PMID:Stunned myocardium and oxygen free radicals--sarcolemmal membrane damage due to oxygen free radicals. 183 72

Oxygen free radicals have been implicated as mediators of cellular injury in ischemia-reperfusion. Since intracellular Ca(2+)-overload has been considered to play a crucial role in ischemia-reperfusion injury, this study was undertaken to examine the effects of oxygen free radicals on Ca(2+)-stimulated Mg(2+)-dependent ATPase activities and ATP-dependent Ca2+ accumulation in rat cardiac sarcolemmal membranes in vitro. Isolated rat heart sarcolemmal membranes were incubated with xanthine (X) + xanthine oxidase (XO) and assayed for Ca(2+)-pump activities. X + XO inhibited the Ca(2+)-pump activities in a time-dependent manner; a significant inhibition of Ca(2+)-stimulated ATPase activity was seen after one min of incubation. Superoxide dismutase showed a protective effect on depression in Ca(2+)-pump activities due to X + XO. To understand the involvement of sulfhydryl groups changes in causing depression of Ca(2+)-pump activities, the effects of oxygen free radicals on heart sarcolemmal sulfhydryl groups were also investigated. Heart sarcolemmal sulfhydryl groups were decreased by X + XO in a time-dependent manner. Superoxide dismutase showed a protective effect on sulfhydryl group depression caused by X + XO. N-ethylmaleimide, a sulfhydryl reagent, showed inhibitory effect on Ca(2+)-pump activities both in a time-, and a dose-dependent manner; dithiothreitol and cysteine prevented changes in Ca(2+)-pump activities caused by N-ethylmaleimide. The inhibitory effect of X + XO on Ca(2+)-pump activities were also prevented by the addition of dithiothreitol or cysteine. A significant correlation between changes in sarcolemmal Ca(2+)-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of heart sarcolemmal Ca(2+)-pump activity by oxygen free radicals. 202 66

Polymorphonuclear (PMN) leukocyte activation is known to result in the production and release of oxygen free radicals and hypochlorous acid. Various clinical conditions are associated with PMN leukocyte stimulation. The present investigation deals with the effects of stimulated PMN leukocytes in the absence and in the presence of scavengers of oxygen free radicals (superoxide dismutase, catalase), hypochlorous acid quencher (methionine), and myeloperoxidase inhibitor (azide) on cardiac function and contractility; blood lactate, gases, and pH levels, blood and cardiac tissue malondialdehyde; and PMN leukocyte chemiluminescence activity in anesthetized dogs. Opsonised zymosan was used for stimulation of PMN leukocytes, and the effects were observed for 2 hours. The dogs were divided into four groups: group I, zymosan; group II, superoxide dismutase + catalase + zymosan; group III, methionine + zymosan; group IV, azide + methionine + zymosan. Zymosan produced a decrease in cardiac function and in indices of myocardial contractility and an increase in systemic and pulmonary vascular resistance. There was a decrease in blood pH and in PMN leukocyte chemiluminescense and an increase in the blood lactate and malondialdehyde. Superoxide dismutase plus catalase and methionine reduced the effect of zymosan on cardiac function and contractility and on blood malondialdehyde, lactate, and pH. The combination of azide and methionine did not prevent the deleterious effects of zymosan on cardiac function and contractility. Cardiac tissue malondialdehyde levels were lower in groups III and IV than in groups I and II which had values similar to each other. Methionine was superior to superoxide dismutase plus catalase in the prevention of the deleterious effects of PMN leukocyte stimulation on the various measured parameters. These results suggest that oxygen free radicals and hypochlorous acid are cardiac depressants and increase systemic and pulmonary vascular resistance in addition to causing tissue damage. Clinical situations with PMN stimulation may result in cardiac depression. The oxygen free radical scavenger and hypochlorous acid quencher may be beneficial in the counteraction of the deleterious effects of PMN leukocyte stimulation on the hemodynamic parameters and cellular integrity.
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PMID:Effect of polymorphonuclear leukocyte-derived oxygen free radicals and hypochlorous acid on cardiac function and some biochemical parameters. 215 22

Numerous studies have indirectly suggested that oxygen-derived free radicals play an important pathogenetic role in the prolonged depression of contractile function observed in myocardium reperfused after reversible ischemia (myocardial "stunning"). In order to provide direct evidence for the oxy-radical hypothesis of stunning, we administered the spin trap, alpha-phenyl N-tert-butyl nitrone (PBN), to open-chest dogs undergoing a 15-min coronary artery occlusion followed by reperfusion. Plasma of local coronary venous blood was analyzed by electron paramagnetic resonance (EPR) spectroscopy. EPR signals characteristic of radical adducts of PBN appeared during ischemia and increased dramatically in the first few minutes after reperfusion. After this initial burst, the production of adducts abated but did not cease, persisting up to 3 h after reflow. The production of PBN adducts after reperfusion was inversely related to collateral flow during ischemia. PBN itself enhanced recovery of contractile function, indicating that the radicals trapped may play a pathogenetic role in myocardial stunning. Superoxide dismutase plus catalase attenuated PBN adduct production and, at the same time, improved recovery of contractile function. Antioxidant therapy given 1 min before reperfusion suppressed PBN adduct production and improved contractile recovery; however, the same therapy given 1 min after reperfusion did not suppress early radical production and did not attenuate contractile dysfunction. After i.v. administration, the elimination half-life of PBN was estimated to be approximately 4-5 h. The results demonstrate that 1) free radicals are produced in the stunned myocardium in intact animals; 2) inhibition of free radical production results in improved contractile recovery; and 3) the free radicals important in causing dysfunction are produced in the first few minutes of reperfusion. Taken together, these studies provide cogent evidence supporting the oxy-radical hypothesis of stunning in open-chest dogs. It is now critical to determine whether these results can be reproduced in conscious animal preparations.
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PMID:Use of spin traps in intact animals undergoing myocardial ischemia/reperfusion: a new approach to assessing the role of oxygen radicals in myocardial "stunning". 216 54

Although oxygen free radicals have been implicated as mediators of cellular injury in myocardial ischemia-reperfusion, the exact nature of defects produced by these radicals is not clear. Because sarcolemmal Ca2+-pump is involved in the efflux of Ca2+ from the cell, this study was undertaken to examine the effects of oxygen free radicals on sarcolemmal ATP-dependent Ca2+ accumulation and Ca2+-stimulated Mg2+-dependent adenosinetriphosphatase (ATPase) activities as well as lipid peroxidation of membrane phospholipids. Isolated rat heart sarcolemmal membranes were incubated with xanthine + xanthine oxidase [a superoxide anion radical (O2-)-generating system], H2O2, or H2O2 + Fe2+ [a hydroxyl radical (HO.)-generating system] and assayed for Ca2+-pump activities. O2- inhibited the Ca2+-pump activities in a time-dependent manner; a significant inhibition of Ca2+-stimulated ATPase activity was seen after 1 min of incubation. Superoxide dismutase showed a protective effect on depression in Ca2+-pump activities caused by O2-.H2O2 inhibited Ca2+-pump activities in a dose-dependent manner; this inhibition was protected by the addition of catalase. HO. depressed the Ca2+-pump activities to a greater extent in comparison with H2O2. Mannitol showed a protective effect on HO.-induced inhibition of Ca2+-pump activities. The promotion of lipid peroxidation by free radicals was evident from increased formation of malondialdehyde. These results indicate that the sarcolemmal membrane is altered on exposure to oxygen free radicals, and this may result in depressing the Ca2+-pump mechanism for Ca2+ efflux from the myocardial cell.
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PMID:Depression of heart sarcolemmal Ca2+-pump activity by oxygen free radicals. 253 32

To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.
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PMID:Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals. 255 Nov 90

In view of the importance of Ca2+-channels in controlling the entry of Ca2+ into the myocardium, this study was undertaken to examine the effects of oxygen free radicals on the binding of Ca2+-channel antagonists in rat heart by employing [3H]-nitrendipine as a ligand. Isolated heart membranes were incubated with xanthine + xanthine oxidase (a superoxide anion radicals generating system), hydrogen peroxide (an activated species of oxygen), or hydrogen peroxide + Fe2+ (a hydroxyl radicals generating system). The assay of the [3H]-nitrendipine binding activity revealed that the maximal number of binding sites (Bmax) were reduced in a time-dependent manner by superoxide radicals without any changes in the binding constant (Kd); a significant reduction of Bmax was seen after incubating membranes with xanthine + xanthine oxidase for a 10-min-period. Superoxide dismutase showed a protective effect on the superoxide radicals induced reduction in Bmax. Both hydrogen peroxide and hydroxyl radicals also depressed the Bmax for [3H]-nitrendipine binding without any significant change in Kd; catalase and mannitol showed protective effects on hydrogen peroxide or hydroxyl radicals induced depression in Bmax, respectively. These results indicate that oxygen free radicals may reduce the number of Ca2+-channels in the cell membrane and this change may contribute towards decreasing the voltage-dependent Ca2+ influx in the cardiac cell.
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PMID:Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart. 255 87


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