Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lysophosphatidylcholine (LPC) accumulates in the heart during myocardial ischemia. This amphiphile accelerates Ca++ flux in cardiac myocytes and may mediate ischemic cell injury. In the present study, we evaluated the effects of LPC on the contractility of cultured neonatal rat heart cells. We also investigated the interactions between LPC and other prominent features of the ischemic milieu, acidosis, and superoxide radical. A photo-optical technique was used to measure the maximum velocities of shortening and relaxation (dS/dt and dR/dt) of cultured cells superfused with 0.1 to 100 mumol/L LPC. LPC, at all concentrations, initially increased dS/dt. After 1 minute, however, dS/dt decreased in a concentration-dependent manner in cells superfused with greater than 20 mumol/L LPC. The effect of LPC on relaxation was also dependent on LPC concentration. dR/dt increased at less than 40 mumol/L LPC but decreased at greater than or equal to 60 mumol/L LPC. Acidosis markedly potentiated LPC-mediated depression in dS/dt and dR/dt. In contrast, superoxide dismutase entirely prevented LPC-mediated depression of contractility. We conclude that whereas brief exposure to LPC stimulates contractility, prolonged exposure to greater than 40 mumol/L LPC depresses dS/dt and dR/dt in cultured myocytes. The depressant effects of LPC on contractility are potentiated by acidosis and superoxide radical. We postulate that LPC accumulation in the myocardium contributes to ischemia-mediated contractile dysfunction.
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PMID:Potentiation of the depressant effects of lysophosphatidylcholine on contractile properties of cultured cardiac myocytes by acidosis and superoxide radical. 215 46

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

Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2(+)-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2(+)-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2(+)-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2(+)-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2(+)-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2(+)-binding activities of the membrane and these effects may be oxygen-radical species specific.
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PMID:Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals. 215 97

The number of strand breaks induced by the combination of chromate and glutathione (GSH) in PM2 DNA was effectively reduced upon addition of the hydroxyl radical scavengers dimethyl sulphoxide (DMSO), formate and benzoate. Administration of catalase also led to a depression of DNA degradation whereas superoxide dismutase (SOD) had very little influence. Essentially the same results were obtained in experiments employing a chromium(V) complex Na4(GSH)4Cr.8H20, which is an intermediate chromium species isolated from the reduction of chromate by glutathione. DNA cleavage was dependent on the presence of iron (FeCl3). When compared with the number of breaks produced by FeCl3 and GSH alone, chromate stimulated the generation of single-strand breaks. These findings suggest that hydroxyl radicals are one ultimate DNA cleaving agent in both reactions. A reaction scheme for the production of hydroxyl radicals is proposed.
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PMID:The DNA cleavage induced by a chromium(V) complex and by chromate and glutathione is mediated by activated oxygen species. 221 25

We have previously demonstrated that induction of the heat-shock response in rats results in improved recovery of isolated Langendorff-perfused rat hearts subjected to low-flow ischemia followed by reperfusion (Currie et al., 1988). The mechanisms underlying this protective effect of heat-shock are uncertain although the protection was associated with enhanced content of the antioxidant enzyme catalase but not superoxide dismutase or glutathione peroxidase (Currie et al., 1988). Various investigators have suggested the importance of improved energy metabolism in determining recovery following ischemia (Pasque and Wechsler, 1984; Haas et al., 1984; Devous and Lewandowski, 1987). We therefore examined, using a working rat heart model subjected to 10 or 15 min zero flow ischemia whether changes in energy metabolites could account for the protective effect of the heat-shock response. Hearts perfused 24 h after induction of heat-shock failed to demonstrate significant improvement of recovery following 10 min ischemia, however recovery was significantly enhanced in hearts reperfused after 15 min ischemia. Ischemia produced a depression in both ATP and creatine phosphate (CP) content whereas a moderate elevation in ADP and AMP and a marked increase in tissue lactate were evident. These changes were unaffected by prior heat-shock treatment. For both durations of ischemia tissue metabolites were determined during early (5 min) and late (30 min) reperfusion. Although partial recovery in high energy phosphates and a return of ADP, AMP and lactate to near-normal levels were evident, no differences in energy products were observed between hearts from normal or heat-shocked animals, in spite of significantly enhanced recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Improved post-ischemic ventricular recovery in the absence of changes in energy metabolism in working rat hearts following heat-shock. 223 33

In the present investigation, the involvement of PMNLs and oxygen free radicals was explored in rats with postischemic perfusion disturbances of the brain. Reversible forebrain ischemia was induced by bilateral clamping of both carotid arteries in combination with hemorrhagic hypotension. This procedure resulted in a reproducible DPH 1 hr after start of recirculation. Neutropenia was induced by sheep ANS. One group received ANS before and a second group immediately after termination of ischemia. Two additional groups received SOD before or immediately after ischemia. Regional postischemic CBF was determined by [14C]iodoantipyrine autoradiography. It was found that CBF significantly improved in cortical structures of animals treated with ANS before ischemia. Treatment with ANS at the end of ischemia had no effect on the postischemic CBF depression. Neither was injection of SOD effective to influence DPH, irrespective whether given before or after ischemia. It is concluded that PMNLs play a role in the development of DPH of the brain, whereas free radical mechanisms seem to be less relevant.
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PMID:Effects of neutrophil depletion and superoxide dismutase on postischemic hypoperfusion of rat brain. 239 65

To investigate the involvement of oxygen free radicals and their scavenger systems in the defenses of compromised hosts against pulmonary infections, we determined superoxide anion (SOA) and superoxide dismutase (SOD; EC 1.15.1.1) concentrations in the blood of compromised hosts and noncompromised hosts, with or without pneumonia. In the compromised hosts without pneumonia (compromised controls), SOD concentrations were lower than in noncompromised hosts (healthy controls). However SOA values in compromised controls did not differ statistically from that in healthy controls. Similar changes were observed in noncompromised hosts with pneumonia. In compromised hosts with pneumonia, SOD concentrations were further decreased by pulmonary infections. By contrast, SOA values were increased in pneumonia. There were, however, no differences in the values for ceruloplasmin among all the groups. The values for alpha 2-macroglobulin and alpha1-antitrypsin were within normal limits in compromised controls but were greater in compromised hosts with pneumonia. These results suggest that a decreased activity concentration of SOD in compromised controls may be partly responsible for the depression of the host's immune defenses.
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PMID:Concentrations of superoxide dismutase and superoxide anion in blood of patients with respiratory infections and compromised immune systems. 244 6

This study investigates the ischemic-time dependency of dysfunction in reversibly ischemic myocardium and the effect of postischemic oxygen free radical scavenging thereupon. In open chest pigs, occlusion of the distal left anterior descending coronary artery (LAD) for 4 (n = 5), 8 (n = 5), or 12 min (n = 5) resulted in paradoxical systolic and diastolic regional function, measured by ultrasonic crystals. With onset of reperfusion, systolic shortening (SS) and diastolic lengthening (DL) normalized completely in the 4- and 8-min groups, followed by a significant decrease to 50% control in the 8-min group. In the 12-min group, recovery of SS and DL was only partial. In two further groups, animals received an intracoronary infusion of either recombinant human superoxide dismutase (SOD, n = 6) or placebo (n = 6), starting with reperfusion after an 8-min LAD occlusion. SOD improved recovery of SS compared with placebo (p less than 0.05), but DL and the depression of SS during later reperfusion were not influenced. Mitochondrial function after 90 min of reperfusion was not impaired in ischemic-reperfused compared to control myocardium. We conclude that the degree of postischemic dysfunction increases with the duration of ischemia. Oxygen free radical scavenging by SOD, starting not before reperfusion, fails to prevent myocardial stunning. Mitochondrial function is intact in such myocardium.
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PMID:Effect of intracoronary superoxide dismutase on regional function in stunned myocardium. 246 55

Cultured type II pneumocyte responses to in vitro normoxia (95% air:5% CO2) or hyperoxia (95% O2:5% CO2) were quantified. Normoxic culture (0 to 96 h) of rabbit type II cells resulted in enhanced cell-monolayer protein and DNA content. During this same time, cellular activities of superoxide dismutase (SOD), catalase, and glutathione peroxidase (GSH Px) decreased. Compared to cultures maintained in normoxia, hyperoxic exposure of cultures resulted in decreased cell-associated protein and DNA content. Exposure to hyperoxia also resulted in cytotoxicity as demonstrated by elevated cellular release of DNA, lactate dehydrogenase (LDH), and preincorporated 8-[14 C]adenine. Cellular catalase and GSH Px activities in hyperoxic cells decreased similarly to normoxic controls. In contrast, cellular SOD activity in hyperoxic cells decreased less than in normoxic cultures. Cellular SOD activity in hyperoxic cultures, when normalized for cellular protein, but not DNA, was greater than normoxic values after 24 to 96 h of exposure. Unlike the decrease in cellular antioxidant enzymes during normoxic and hyperoxic culture, cellular LDH activity increased during both these exposures. Cellular LDH activity in 24 to 96 h hyperoxia-exposed cells increased to a lesser extent than normoxic controls. The extent of depression in LDH activity was dependent on whether the activity was normalized for cellular protein or DNA. Type II pneumocytes, which normally undergo hyperplasia and hypertrophy during hyperoxia in vivo, exhibited oxygen sensitivity in vitro. Exposure of type II cells to hyperoxia in vitro resulted in alterations in cellular SOD and LDH activities, but recognition of such changes were dependent on whether enzymatic activities were normalized for cellular DNA or protein.
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PMID:Responses of type II pneumocyte antioxidant enzymes to normoxic and hyperoxic culture. 250 12

In the present work, an experimental system was designed to study superoxide anion radical, implicated as the cause of vascular dilatation. To circumvent its direct effect, we employed a two-bath system. When the endothelial cells (EC) were exposed to electrical field stimulation (EFS) or to a hypoxanthine-xanthine oxidase system in bath A plus its physiological buffer solution suffused on a helical strip of cat basilar artery in bath B, the contraction to 5-hydroxytryptamine (5-HT) was depressed to approximately 40-50% of the control value. The reduction was not elicited on EFS in a state of calcium deficiency or in the absence of EC. The depression could be prevented by pretreatment with superoxide dismutase (SOD), but not with an effective dose of catalase, dimethyl sulfoxide (DMSO), mannitol, or indomethacin. The percent depression of contraction was paralleled by an increase in SOD-inhibitable cytochrome c reduction, which was not associated with cyclic guanosine 3',5'-monophosphate formation. These results suggest that superoxide-dependent relaxing factor is released from EC differently than the endothelium-derived relaxing factor mediated by acetylcholine.
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PMID:Release of superoxide-dependent relaxing factor(s) from endothelial cells. 255 45


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