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)

Elementary Na+ currents were recorded at 19 degrees C in cell-attached and inside-out patch-clamp experiments to study the influence of the vasoactive peptide angiotensin II (A II) and of the diacylglycerol analogue OAG (1-oleoyl-2-acetyl-sn-glycerol) on open probability and gating properties of single cardiac Na+ channels from cultured neonatal rat cardiocytes. Treating the cardiocytes with A II caused Na+ channel activation: reconstructed peak INa increased to 137 +/- 17.5% of control at 3 mumol/liters and to 176 +/- 42% at 30 mumol/liter. This NPo increase developed without major changes in open state and burst activity, even at 30 mumol/liter. OAG (6 mumol/liter) did not mimic this A II action. By contrast, OAG treatment of the cardiocytes had the opposite effect on NPo and diminished reconstructed peak INa to 67 +/- 4.9% of the control. The putative protein kinase C inhibitor staurosporine (0.2 mumol/liter) abolished this INa depression and led to a normalization of NPo. OAG had the same effect on isolated Na+ channels. Exposure of the cytoplasmic surface of inside-out patches to 1 mumol/liter OAG reversibly depressed, in the simultaneous presence of 50 mumol/liter Mg-ATP, the reconstructed peak INa to 40 +/- 9.7% of the control but left unit, tau open and burst activity unaffected. No NPo depression was obtained in the absence of Mg-ATP indicating that Mg-ATP may serve as phosphate donor. Obviously, after phosphorylation by protein kinase C, cardiac Na+ channels attain a reduced open probability but appear to preserve their kinetic properties.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Opposite effects of angiotensin II and the protein kinase C activator OAG on cardiac Na+ channels. 133 16

1. The hemolytic effect of L-sorbose on canine erythrocytes characterized by inherited high Na, K-ATPase activity and a high potassium concentration (HK RBCs) was compared with that on normal canine erythrocytes (LK RBCs). 2. Dogs having HK RBCs (HK dogs) revealed no clinical and hematological changes after administration of L-sorbose, whereas normal dogs (LK dogs) developed severe hemolytic anemia associated with hemoglobinuria and marked decreases of erythrocyte ATP concentrations. 3. In vitro, L-sorbose induced hemolysis in LK RBCs along with the depression of both ATP and lactate formation in these cells, but not in HK RBCs. The inhibition of glycolysis by L-sorbose in LK RBCs, however, was not observed when glucose-6-phosphate was used as a substrate instead of glucose. 4. These results suggest that the disparity of susceptibility to sorbose-induced hemolysis may be due to the difference in erythrocyte metabolism between HK and LK RBCs, especially the high activity of hexokinase in HK cells, which was 2-fold greater than that in LK RBCs.
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PMID:L-sorbose does not cause hemolysis in dog erythrocytes with inherited high Na, K-ATPase activity. 135 45

There is no established treatment specifically aimed at protecting or restoring cardiac energy metabolism, which is greatly impaired by ischaemia. Even after reperfusion, myocardial content of ATP remains low for more than 72 h. Long-term post-ischaemic dysfunction and irreversibility of ischaemic damage have been associated with low ATP content. Evidence that the pentose sugar ribose stimulates ATP synthesis and improves cardiac function led us to test the possibility that ribose increases tolerance to myocardial ischaemia in patients with coronary artery disease (CAD). 20 men with documented severe CAD underwent two symptom-limited treadmill exercise tests on 2 consecutive days; we postulated that the ischaemia induced might bring about changes in ATP metabolism lasting for several days. Patients whose baseline tests showed reproducibility were randomly allocated 3 days of treatment with placebo or ribose 60 g daily in four doses by mouth. Exercise testing was repeated after treatment on day 5. At that time mean (95% confidence interval) treadmill walking time until 1 mm ST-segment depression was significantly greater in the ribose than in the placebo group (276 [220-331] vs 223 [188-259] s; p = 0.002). The groups did not differ significantly in time to moderate angina. In the ribose-treated group the changes from baseline to day 5 in both time to ST depression and time to moderate angina were significant (p less than 0.005), but these changes were not significant in the placebo group. In patients with CAD, administration of ribose by mouth for 3 days improved the heart's tolerance to ischaemia. The presumed effects on cardiac energy metabolism offer new possibilities for adjunctive medical treatment of myocardial ischaemia.
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PMID:Effects of ribose on exercise-induced ischaemia in stable coronary artery disease. 135 76

Evidence has been put forth that a number of human and experimental cardiomyopathies are associated with a lower myocardial carnitine content. This study was performed to test the hypothesis that the correction of carnitine derivative, propionyl-L-carnitine (PLC), may improve cardiac function. Repeated administration of PLC was compared to saline with respect to cardiac function in rats with pressure-overload cardiac hypertrophy and low myocardial carnitine levels. Cardiac hypertrophy was induced by abdominal aorta constriction in rats. Separate groups of rats were used for (a) determination of myocardial carnitine content, (b) evaluation of in vivo hemodynamics, and (c) evaluation of performance and metabolic state of Langendorff perfused hearts. Results showed the following: (i) The myocardial carnitine content was inversely correlated to cardiac hypertrophy (r = 0.68, p less than 0.05) and PLC treatment (50 mg/kg i.a. for 4 days) restored it to normal values (ii) The PLC effect on cardiac function was significantly and directly related to cardiac hypertrophy [correlations between heart weight and percent changes in cardiovascular parameters: cardiac output (CO), p less than 0.001; cardiac work (CW), p less than 0.01, stroke volume (SV) and stroke work (SW), p less than 0.02]. In animals with heart weight greater than 1,400 mg, the effect of PLC on CO, CW, SV, SW, and total peripheral resistance (TPR) was significantly different from that of saline (CO, CW, SV, and SW, p less than 0.005 each; TPR, p less than 0.05). The effect was observed 24 h after the first PLC administration and significantly diminished following a 4 day suspension of the treatment. (iii) Perfused hearts from PLC-treated rats displayed a significantly lower left ventricular end-diastolic pressure (p less than 0.01) and greater relaxation rate (p less than 0.05) than those from control rats. Moreover, in PLC-treated hearts, the content of creatine phosphate, ATP, and total adenine nucleotides (ATP+ADP+AMP; TAN) was significantly increased (CP, p less than 0.05; ATP and TAN, p less than 0.01 vs. control). These data show that PLC exerts a stimulatory activity on hearts with hypertrophy and low carnitine content, implying that carnitine deficiency may contribute to the depression of cardiac function in this model.
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PMID:Hemodynamic and metabolic activities of propionyl-L-carnitine in rats with pressure-overload cardiac hypertrophy. 138 36

A study is presented on the role of F0 and F1 subunits in oligomycin-sensitive H+ conduction and energy transfer reactions of bovine heart mitochondrial F0F1 H(+)-ATP synthase. Mild treatment with azodicarboxylic acid bis(dimethylamide) (diamide) enhanced oligomycin-sensitive H+ conduction in submitochondrial particles containing F1 attached to F0. This effect was associated with stimulation of the ATPase activity, with no effect on its inhibition by oligomycin, and depression of the 32Pi-ATP exchange. The stimulatory effect of diamide on H+ conduction decreased in particles from which F1 subunits were partially removed by urea. The stimulatory effect exerted by diamide in the submitochondrial particles with F1 attached to F0 was directly correlated with a decrease of the original electrophoretic bands of a subunit of F0 (F0I-PVP protein) and the gamma subunit of F1, with corresponding formation of their cross-linking product. In F0 liposomes, devoid of gamma subunit, diamide failed to stimulate H+ conduction and to cause disappearance of F0I-PVP protein, unless purified gamma subunit was added back. The addition to F0 liposomes of gamma subunit, but not that of alpha and beta subunits, caused per se inhibition of H+ conduction. It is concluded that F0I-PVP and gamma subunits are directly involved in the gate of the F0F1 H(+)-ATP synthase. Data are also presented indicating contribution to the gate of oligomycin-sensitivity conferral protein and of another protein subunit of F0, F6.
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PMID:Role of F0 and F1 subunits in the gating and coupling function of mitochondrial H(+)-ATP synthase. The effect of dithiol reagents. 138 61

To determine the effects of dietary protein level on cardiac and hepatic mitochondrial oxidative phosphorylation, chicks were fed on semi-purified diets of different protein levels (7, 25, 43 and 61% of metabolizable energy content) for 7, 14 and 21 d. All diets were formulated to contain equivalent fat, mineral and vitamin contents on a gross energy basis. Cardiac and hepatic mitochondrial oxidative phosphorylation rates were assessed polarographically with pyruvate and malate as substrates. Cardiac mitochondria isolated from chicks fed on a 43 or 61% protein-energy diet for 7 d exhibited significantly reduced ADP:oxygen (ADP:O) ratios when compared with mitochondria isolated from chicks fed on a lower-protein-energy diet. Feeding low- (7%) protein-energy diets for 14 d resulted in a relatively increased ADP:O ratio in the heart. Responses of ADP:O ratios to protein level in hepatic mitochondria showed more dependency on protein level than in heart muscle; at all feeding periods the ADP:O ratio decreased with an increase in protein level. As a result, ATP synthesized in the liver, expressed as nmol/mg mitochondrial protein per min, significantly decreased with increased dietary protein level. A parallel correlation was observed, in chicks fed on diets with different levels of protein, between ADP:O ratio for liver mitochondria and body fat. These results suggest that the reduction in oxidative phosphorylation in the heart and liver of animals fed on a higher protein-energy diet may partly contribute to the depression of body fat.
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PMID:Dietary protein level alters oxidative phosphorylation in heart and liver mitochondria of chicks. 139 Jun 19

1. Orthophosphate (P(i), 0.1-2.0 mM) was photogenerated within the filament lattice of isometrically contracting glycerinated fibres of rabbit psoas muscle at 10 and 20 degrees C. The P(i) was produced by laser flash photolysis of the photolabile compound 1-(2-nitrophenyl)ethylphosphate (caged P(i)). Caged P(i) caused a depression of tension that was much smaller than that caused by P(i). 2. Photolysis of caged P(i) produced a decline in isometric force composed of four phases: phase I, a lag phase (e.g. 1-4 ms at 10 degrees C) during which force did not change; phase II, an exponential decline by as much as 20% of the pre-pulse force; phase III, a partial force recovery (0-3% of the pre-pulse force); and phase IV, a further slow (0.5-3 s) decline to the steady value. Phases I, III and IV were largely independent of [P(i)] and are likely to be indirect effects caused by the caged P(i) photolysis. 3. Both the rate and amplitude of phase II depended markedly on [P(i)]. The amplitude of phase II was similar to the reduction of steady-state force by P(i). The rate of phase II increased with increasing temperature and [P(i)]. At high [P(i)] the rate began to saturate, and approached limits of 123 s-1 at 10 degrees C and 194 s-1 at 20 degrees C. 4. The rate of phase II was independent of sarcomere overlap, while the amplitude was proportional to tension at partial filament overlap. A control experiment using caged ATP showed that phase II was not produced by the photolytic by-products or the light pulse. The results suggest that phase II is associated with the force-generating transition of the cross-bridge cycle. 5. Sinusoidal length oscillations at 0.5 and 2 kHz were used to measure muscle stiffness during phase II. Stiffness declined in a single exponential phase, with the same time course as phase II of the tension transient. The change in stiffness was 83 +/- 6% (mean +/- S.E.M., n = 10, 0.5 kHz) of the change in tension when both signals were normalized to their pre-flash values. 6. Analysis of the data shows that two steps are involved in force generation and P(i) release. The non-force exerting AM-ADP-P(i) cross-bridge state first isomerizes to form a force-exerting cross-bridge state (AM'-ADP-P(i)). P(i) is then released to form a second force-generating state, AM'-ADP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Reversal of the cross-bridge force-generating transition by photogeneration of phosphate in rabbit psoas muscle fibres. 140 12

We correlated the effects of high volumes of K+ cardioplegic solution on myocardial structure and function in 16 dogs following open-heart surgery. Eight animals received high volume potassium cardioplegic solution (25 cc/kg body weight, every 30 min) during 90 min of ischemic arrest (HVK-C group). The others received sufficient cardioplegic solution to maintain complete electrical arrest as defined by voltage monitoring criteria (VM group). Cardiac index (CI), left ventricular stroke work index (LVSWI), and myocardial contractility (dp/dt) were determined before arrest and after 90 min of ischemia and 45 min of reperfusion. Biopsies were taken for EM ultrastructure and ATP estimation. Morphometric analysis of EM micrographs found increased volume of damaged mitochondria (DMR) (p less than 0.025), damaged myofibrils (DMF) (p less than 0.001), intermyofibrilar edema (p less than 0.005), T-tubule and sarcoplasmic reticulum (p less than 0.05) in the HVK-C group. Left ventricular (LV) function was more depressed in animals receiving HVK-C. CI decreased by 1.8 +/- 0.4 l/min/square meter (p less than 0.01), LVSWS fell by 3.3 +/- 0.8 gm-m/beat/Kg (p less than 0.01), dp/dt decreased by 684 +/- 135 (p less than 0.0025). ATP decreased by 26% in HVK-C and by 12% in VM group (0.1 less than p less than 0.05). Structural damage (scores of injured volume of mitochondria and myofibrils) correlated with post-ischemic depression of LV function (Cardiac output and myocardial contractility), r = -0.72 and -0.66 (p less than 0.001 and 0.004).
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PMID:Morphometric analysis on myocardial injury related to the use of high volume potassium cardioplegic solution during ischemic arrest. 140 9

Intracellular free Mg2+ concentration ([Mg2+]i) was measured in isolated single fibres of Xenopus muscle using the fluorescent Mg2+ indicator furaptra. In resting muscle the [Mg2+]i was 1.7 mM in a Mg(2+)-free Ringer solution. There was no significant change in [Mg2+]i over 2 h in Mg(2+)-free Ringer solution. Elevating extracellular [Mg2+] to 40 mM for 5 min caused a small rise (0.13 mM) in [Mg2+]i. There was no detectable rise in [Mg2+]i after 5 min in Na(+)-free Ringer solution. These results suggest that the membrane is relatively impermeable to Mg2+ and that there was no detectable Na(+)-Mg2+ exchange over 5 min. When muscle fibres were fatigued by repeated tetani continued until force declined to about 40% of control, [Mg2+]i showed characteristic changes. During the early period of fatigue when force first showed a small decline and then became almost stable, [Mg2+]i was unchanged; during the final period of fatigue when force declined more rapidly, [Mg2+]i increased by 0.8 mM. Recovery of [Mg2+]i took about 30 min. Recovery of force was complex: tetanic force first declined (post-contractile depression) and then slowly recovered to control. Since the minimum force occurred at about the time when [Mg2+]i had recovered, it seems unlikely that post-contractile depression is caused by elevated [Mg2+]i. Rigor, produced by inhibiting oxidative phosphorylation and glycolysis, was associated with a larger increase (1.6 mM) in [Mg2+]i than fatigue. The rise in [Mg2+]i during fatigue and metabolic blockade could be explained as release of Mg2+ normally bound to ATP. A model of the metabolic changes and the resulting increase in [Mg2+]i explains our results reasonably well.
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PMID:Myoplasmic Mg2+ concentration in Xenopus muscle fibres at rest, during fatigue and during metabolic blockade. 141 55

Defibrotide (DEF), a compound previously found to stimulate vascular prostacyclin (PGI2) formation, has been investigated in an experimental model of septic shock. Anesthetized pigs were subjected to i.v. infusion of lipid A (1.5 mg/kg per hr for 4 hr). DEF (50 mg/kg per hr) or vehicle were infused i.v. throughout the experiments, starting 1 hr prior to lipid A. Two out of 7 pigs receiving vehicle survived lipid A infusion for 4 hr, whereas 6 out of 7 DEF treated animals survived this period (P less than 0.05). DEF delayed the shock-induced depression of platelet count and preserved platelet secretory function (collagen-induced ATP-secretion). DEF increased plasma PGI2 by 45% (P less than 0.05) during lipid A infusion and tended to reduce thromboxane levels. DEF did not change eicosanoid formation in sham-shock pigs (n = 4 per group). In vivo treatment with DEF significantly increased the stimulatory effect of bradykinin (1 microM) and arachidonic acid (100 microM) on PGI2 formation ex vivo of mesenteric and iliac artery segments. The improvement of survival in lipid A-induced shock by DEF may be related to an enhancement of vascular PGI2 generation, potentially due to a reduction of shock-induced platelet activation and microcirculatory dysfunction.
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PMID:Favourable effect of defibrotide in lipid A-induced shock in pigs. 142 20


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