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

Phosphate (Pi)-induced depression in cardiac mitochondrial function was studied using mitochondria isolated by two different procedures which purportedly yield two distinct populations. Subsarcolemmal mitochondria (SLM) exhibited an enhanced sensitivity to 20 mM Pi with respect to oxidative phosphorylation. Thus, a significant depression in oxidative phosphorylation in this population was seen following only 1-min treatment, whereas interfibrillar mitochondria (IFM) were unaffected. Both populations showed a similar response to 5-min treatment with Pi. The Pi-induced depression in respiration was partially, although significantly, reversed by a 50 microM concentration of the calcium antagonist verapamil, an observation which suggests a contribution of calcium to the Pi-induced defect in respiration. Pi also produced a potent inhibition of ADP uptake in both mitochondrial populations, which was in close agreement to Pi-induced modification of low amplitude shrinkage-swelling responses following ADP addition. Both of these parameters were unaffected by verapamil. Our results show an enhanced sensitivity of SLM to a verapamil-sensitive Pi-induced depression in oxidative phosphorylation. However, the potent, verapamil-insensitive decrease in adenine nucleotide translocase activity by Pi demonstrates that calcium is likely only partially involved in Pi-induced depression in oxidative phosphorylation and that a further partial contribution arises from a decrease in adenine nucleotide translocase activity.
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PMID:Effect of verapamil on phosphate-induced changes in oxidative phosphorylation and atractyloside-sensitive adenine nucleotide translocase activity in two populations of rat heart mitochondria. 255 33

Initial Polytron treatment with subsequent exposure to the bacterial proteinase Nagarse has been shown to result in the isolation of two distinct populations of cardiac mitochondria, subsarcolemmal and interfibrillar mitochondria, respectively. Although these populations have been shown to possess distinct biochemical properties, few studies have been reported which document the potential differences in their response to pathological insult. We therefore examined the effect of acute hypoxia with or without reoxygenation as well as treatment with phosphate on oxidative phosphorylation on both groups of mitochondria. Freshly-isolated interfibrillar mitochondria (IFM) exhibited significantly higher respiratory values, with the exception of the ADP:O ratios, than subsarcolemmal mitochondria (SLM). With pyruvate-malate as respiratory substrate, 40 minutes hypoxia alone produced no effect on SLM whereas a stimulation in respiration was seen in IFM. A 40-minute reoxygenation period depressed the oxidative phosphorylation rate in SLM whereas it was stimulated in IFM. These treatments did not produce any effect in either population when succinate was the substrate of choice. Because of the latter observation, the possibility that increased lability of complex I of the electron transport chain accounted for the differences associated with NAD-linked substrates was studied by assessing NADH oxidation of sonicated mitochondria following the treatments. SLM exhibited enhanced permeability to exogenous NADH as well as increased sensitivity to sonication following either hypoxia or hypoxia/reoxygenation compared to IFM. Compared to hypoxia/reoxygenation, increasing concentrations of phosphate (5-15 mM) produced a marked depression in oxidative phosphorylation of SLM whereas IFM were relatively resistant. The toxic effects of phosphate were much more evident with pyruvate-malate as substrates; with succinate, oxidative phosphorylation of IFM was not depressed by phosphate whereas only a slight depression was observed with SLM. The latter population similarly exhibited reduced NADH oxidation following phosphate treatment whereas IFM were unaffected. Our studies show a differential sensitivity of two mitochondrial populations to hypoxia/reoxygenation, and, more markedly to phosphate. Since these effects were much less pronounced with succinate-linked respiration and since they were associated with defective NADH oxidation in SLM, it is suggested that the differences between the two populations may be accounted for by the increased lability of complex I of SLM due to hypoxia/reoxygenation or phosphate.
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PMID:Acute effects of hypoxia and phosphate on two populations of heart mitochondria. 260 32

1. The effect of 100 microM (20 micrograms ml-1) of D,L-carnitine was studied on the isolated heart of the rat subjected to 30 min of low flow ischaemia followed by reperfusion. 2. In untreated hearts (n = 30) ischaemia produced an almost total loss of contractility (P less than 0.05 compared with non-ischaemic time control) which was accompanied by an increase in resting tension of approximately 235% (P less than 0.05). Ventricular arrhythmias developed during ischaemia in 100% (P less than 0.05) of untreated hearts studied. Following reperfusion, untreated hearts recovered 16.3% of contractile function and demonstrated a 60% elevation in resting tension. The incidence of reperfusion-associated ventricular fibrillation was 60%. 3. Carnitine treatment produced no effect on either the contractile depression or the elevation in resting tension during ischaemia but did significantly decrease the incidence of arrythmias at the termination of ischaemia to 63.3% (n = 30, P less than 0.05). In the presence of carnitine, contractile recovery at the end of reperfusion was significantly increased to 30.2% (n = 10, P less than 0.05) and the elevation in resting tension was decreased to 30% (n = 10, P greater than 0.05). The incidence of ventricular arrhythmias during reperfusion was significantly reduced by carnitine. 4. Two populations of mitochondria, subsarcolemmal (SLM) and interfibrillar (IFM) isolated at the end of the ischaemic period exhibited an overall increase in oxidative phosphorylation rates as well as uncoupled oxygen consumption; both phenomena were more pronounced with IFM. Carnitine generally potentiated this response. A 29% and 38% inhibition in atractyloside-sensitive ADP uptake was observed in SLM and IFM, respectively, following ischaemia, which was partially prevented by carnitine. 5. After 10min of reperfusion, adenosine diphosphate (ADP) uptake in SLM was further reduced to 55% of control whereas with IFM, uptake was not different from that seen at the end of ischaemia. Mitochondria isolated from hearts after 30 min of reperfusion revealed a significantly depressed oxidative phosphorylation as well as ADP/ATP translocase activity. These defects were partially reversed in hearts perfused with carnitine. 6. Our study demonstrates that D,L-carnitine protects the rat isolated heart against injury associated with ischaemia and reperfusion through a mechanism associated with improved mitochondrial function.
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PMID:Effect of D,L-carnitine on the response of the isolated heart of the rat to ischaemia and reperfusion: relation to mitochondrial function. 261 94

In anaerobically grown yeast cells which lack functional mitochondria, the presence of diethylstilbestrol (DES) depressed glycolysis. The addition of the inhibitor markedly increased the cellular concentration of glycolytic intermediates which are formed prior to the pyruvate kinase step as well as to bring about an increase in the [ATP]/[ADP] ratio. Under these conditions an 18 fold decrease in the mass action ratio for pyruvate kinase [( pyruvate] [ATP]/[phosphoenolpyruvate] [ADP]) was noted, however, there was little if any effect on the other glycolytic enzymes. These results suggest that the depression of anaerobic glycolysis caused by DES results from a blockage at the level of the regulatory enzyme pyruvate kinase through a modification of its intracellular environment.
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PMID:Inhibition of glycolysis induced by diethylstilbestrol in anaerobically grown yeast. 269 93

We examined mitochondrial oxidative function 5 minutes and 2 hours after a gradual asphyxial insult in newborn lambs. We subjected 16 ventilated newborn lambs to 75-90 minutes of hypoxia and hypercarbia that resulted in bradycardia and systemic hypotension over the final 15 minutes of the insult. At the end of asphyxia, the lambs were resuscitated and returned to control ventilator settings. Samples of brain were removed 5 minutes (n = 8) and 2 hours (n = 8) after asphyxia. Each group of eight lambs was subdivided into those less than 3 or greater than 3 days old to evaluate the effect of age on postasphyxia mitochondrial function. After classification into nonsynaptic and synaptic mitochondria, mitochondrial respiration (oxygen consumption) was measured using five different substrates. Data from asphyxiated lambs were compared with that from a control group of ventilated nonasphyxiated lambs (n = 8). In the lambs less than 3 days old, there was significant depression of mean +/- SEM nonsynaptic mitochondrial state 3 (adenosine diphosphate-dependent) respiration to 29.5 +/- 5.2% of control with four of the five substrates and of state 4 respiration to 33.7 +/- 0.9% of control with three of the five substrates 5 minutes after asphyxia. By 2 hours after asphyxia, mean +/- SEM nonsynaptic mitochondria state 3 respiration increased to 70.4 +/- 6.4% of control while state 4 respiration increased to 58.2 +/- 4.5% of control. In contrast, lambs greater than 3 days old exhibited no inhibition of nonsynaptic mitochondrial function after asphyxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mitochondrial function after asphyxia in newborn lambs. 271 9

The function of renal cortical mitochondria isolated from rats with cyclosporine nephrotoxicity was studied. Renal cortical mitochondria were isolated from 5 male Fischer rats after 14 days of daily intraperitoneal administration of CsA, 25 mg/kg body wt. Compared with the mitochondrial function of 5 pair-fed control rats receiving vehicle alone, state 3 respiration (ADP-dependent) using several substrates was mildly depressed only with pyruvate-malate supported respiration (27 +/- 3 vs. 36 +/- 2 nmol O2/min/mg protein; P less than 0.05). The Ca2+ accumulation rate was slightly reduced (354 +/- 14 vs. 416 +/- 18 nmol/min/mg protein; P less than 0.025) while the cytochrome enzyme concentrations were not different from controls. Respiratory control ratios were not affected (CsA group: 9.5 +/- 2.8, control group: 8.9 +/- 2.3; glutamate-malate as substrates). These minor alterations in mitochondrial function occurred in the presence of severe depression in the glomerular filtration rate and renal morphologic changes commonly seen with CsA administration. Moreover, there was no increase in enzymuria. These results indicate that CsA has minor effects on the respiratory function of renal cortical mitochondria. The severe depression in the glomerular filtration rate is out of proportion to these minor alterations in mitochondrial function. These findings argue against a prominent role for a direct toxic action of CsA on tubular cells in the pathogenesis of acute cyclosporine-induced renal dysfunction.
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PMID:Renal cortical mitochondrial integrity in experimental cyclosporine nephrotoxicity. 274 85

Previous studies have shown that haemorrhage in Lassa fever is associated with abnormal in vitro platelet aggregation and a high mortality. In Sierra Leone we studied platelet aggregation in healthy local subjects, patients with laboratory-confirmed Lassa fever and febrile patients in whom Lassa virus infection was excluded. There were no significant differences in the mean platelet counts of these groups. Patients with fulminant Lassa virus infection showed a gross depression of in-vitro platelet responsiveness to 1 and 5 microM ADP and 4 micrograms/ml collagen compared to other groups (P = 0.0004-0.0008 when compared to healthy controls, P = 0.002-0.0008 when compared to mild Lassa fever patients). When plasma samples from five of these patients were mixed 1:1 with control platelet-rich plasma, a marked inhibition of ADP-induced aggregation was observed. No inhibitory activity was detected in plasma obtained from healthy subjects or febrile control patients. The presence of inhibitor was strongly associated with the occurrence of haemorrhage (P = 0.03), depression of platelet aggregation (P = 0.004) and severity of Lassa fever (P = 0.007).
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PMID:A plasma inhibitor of platelet aggregation in patients with Lassa fever. 277 59

Eicosapentaenoic acid (EPA), the precursor fatty acid of three series of prostaglandins, has been reported to have an antiatherothrombotic potential. We gave highly purified EPA in a soft capsule (90% ethylester form of EPA; EPA-E) to 6 healthy male volunteers for 4 weeks. After the administration of 900 mg/day of EPA-E for two weeks or longer, a significant reduction in plasma beta thromboglobulin level was observed, and after 4 weeks' administration, significantly blunted pressor responsiveness to infused angiotensin II was observed. These changes were not observed 4 weeks after EPA-E had been discontinued. After 4 weeks' ingestion of EPA-E, the platelet count, mean platelet volume, platelet aggregation with adenosine diphosphate or collagen, plasma recalcification time, prothrombin time, plasma antithrombin III, fibrinogen or plasmin concentrations, serum concentrations of total cholesterol, triglycerides, total phospholipid, nonesterified fatty acid or high-density lipoprotein cholesterol were unchanged. From the data presented it can be said that EPA-E causes a mild depression of vascular contractility and of platelet aggregability in vivo and exerts a beneficial influence on several cardiovascular factors.
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PMID:Effects of highly purified eicosapentaenoic acid on plasma beta thromboglobulin level and vascular reactivity to angiotensin II. 282 70

Transducin is the substrate for a pertussis toxin-catalyzed ADP-ribosylation in isolated retinal rod disk membranes [(1984) J. Biol. Chem. 259, 23-26]. The effects of the toxin on the light responses of intact dark-adapted rods were studied. Applied close to a rod outer segment in a retinal slice, pertussis toxin depolarized the rod by a few millivolts and produced a long-lasting depression of light responses, effects which depended on penetration of toxin into rods. Nicotinamide, an inhibitor of ADP-ribosylation, not only blocked the action of the toxin, but also reversed the effects once established. The action of nicotinamide itself on rods indicates the presence of endogenous ADP-ribosyltransferases which may constitute a control system modulating phototransduction. Inhibition of phospholipase C by neomycin had only transient effects indicating that the cGMP, rather than a phosphoinositide, pathway is primary in vertebrate phototransduction. Rapid reversal of pertussis toxin action suggests possible clinical applications of nicotinamide or congeners to the treatment of disease caused by ADP-ribosylating bacterial toxins.
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PMID:Block of light responses of salamander rods by pertussis toxin and reversal by nicotinamide. 283 Oct 82

The pathophysiological mechanisms of altered transmembrane potentials in diseased human atria were investigated in 20 patients who were divided into group A (normal) and group B (diseased). The electrophysiological data of right atrial tissues measured with glass microelectrodes included maximum diastolic potentials (MDP), action potential amplitudes (APA) and action potential durations at the time required for 50% repolarization (ADP 50%) and 75% repolarization (APD 75%). The sarcolemma isolated from atrial tissues was used for determination of the sarcolemmal Na+-K+ ATPase activities. Anionic molecular sites distributed in the sarcolemmal complex were characterized by cationized ferritins (CF). The electrophysiological data in groups A and B were: MDP -80.74 +/- 1.94 mV and -44.54 +/- 6.24 mV, APA 92.72 +/- 9.25 mV and 57.74 +/- 10.85 mV, APD 50% 42.48 +/- 6.63 msec and 210.34 +/- 36.38 msec and APD 75% 56.47 +/- 8.55 msec and 281.66 +/- 42.18 msec respectively. The difference in the Na+-K+ ATPase activities between groups A (15.37 +/- 0.46 mumole Pi/mg/hr) and B (12.55 +/- 0.4 mumole Pi/mg/hr) was highly significant. CF molecules were frequently seen to be more irregularly and loosely distributed in the sarcolemmal surfaces of group B atrial myocytes. Based on these results we conclude that depression of the sarcolemmal Na+-K+ ATPase activity and derangement of the anionic binding sites in the sarcolemmal surfaces play an important role in altering transmembrane potentials in diseased human atria.
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PMID:Pathophysiological mechanisms of altered transmembrane potentials in diseased human atria. 302 20


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