scholarly journals The effects of acetylcolletotrichin on the mitochondrial respiratory chain

1974 ◽  
Vol 138 (3) ◽  
pp. 415-423 ◽  
Author(s):  
Bernard Foucher ◽  
J. B. Chappell ◽  
J. D. McGivan
Keyword(s):  
Mitochondrial Respiratory Chain ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Oxidative Activity ◽  
Detectable Effect ◽  
Succinate Oxidation ◽  
Kidney Mitochondria ◽  
Liver And Kidney ◽  
High Concentrations ◽  
Oxidation System

1. Acetylcolletotrichin is a phytotoxic compound that has been isolated from the culture medium of the fungus Colletotrichum capsici (Grove et al., 1966). 2. With isolated liver and kidney mitochondria acetylcolletotrichin markedly inhibited the oxidation of succinate and those substrates with NAD-linked dehydrogenases, but did not inhibit the oxidation of ascorbate in the presence of tetramethyl-p-phenylenediamine. In this respect its action was similar to that of antimycin A. 3. Acetylcolletotrichin differed from antimycin in that, even at high concentrations which produced a maximal inhibitory effect, its action was partially reversed by uncoupling agents. Also acetylcolletotrichin had no detectable effect on the oxidative activity of blowfly flight-muscle mitochondria and was not very effective with heart mitochondria. 4. Acetylcolletotrichin inhibited the oxidative activity of liver mitochondria more markedly when respiration was stimulated by ADP together with phosphate and was less effective when respiration was stimulated by uncoupling agents. 5. There was an unusual interaction between the succinate oxidation system and the oxidation of glutamate together with malate. Thus, glutamate together with malate, even in the presence of rotenone, markedly decreased the effectiveness of acetylcolletotrichin in inhibiting succinate oxidation. 6. These effects were paralleled in the observed redox changes of cytochrome c. 7. The unusual behaviour of the cytochromes b in the presence of acetylcolletotrichin is described, and it is suggested tentatively that this inhibitor acts between cytochromes b with absorption maxima at 30°C of approximately 560 and 565nm.

scholarly journals Influence of ubiquinone on the inhibitory effect of adriamycin on mitochondrial oxidative phosphorylation

1984 ◽  
Vol 217 (2) ◽  
pp. 493-498 ◽  
Author(s):  
H Muhammed ◽  
C K R Kurup
Keyword(s):  
Oxidative Phosphorylation ◽  
Rat Heart ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Oxidative Activity ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Succinate Oxidation ◽  
Exogenous Addition

The inhibition of succinate oxidation in both heart and liver mitochondria by the cardiotoxic anticancer antibiotic adriamycin in vitro was reversed to a large extent by exogenous ubiquinone-45. Inhibition of the oxidation of NAD+-linked substrates in heart and liver mitochondria responded differently to ubiquinone, the inhibition being reversed only in liver organelles. Administration of adriamycin inhibited oxidative phosphorylation in rat heart, kidney and liver mitochondria, the inhibition being highest in the heart organelles (about 50% for both NAD+-linked substrates and succinate). Exogenous addition of ubiquinone to mitochondria isolated from drug-treated animals did not reverse the inhibition. Administration of ubiquinone along with adriamycin did not change effectively the pattern of drug-mediated decrease in oxidative activity of the organelles, particularly in the heart.

Effects of protamine and strophanthin on mitochondrial potassium, sodium and water

1960 ◽  
Vol 199 (4) ◽  
pp. 653-656
Author(s):  
Leonard Share
Keyword(s):  
Rat Liver ◽  
Sodium Concentration ◽  
Water Metabolism ◽  
Intact Cells ◽  
Kidney Mitochondria ◽  
Potassium Sodium ◽  
Isolated Mitochondria ◽  
Liver And Kidney ◽  
Uncoupling Of Oxidative Phosphorylation ◽  
High Concentrations

A study was made of the effects of certain agents, which inhibit potassium transport in intact cells, on the potassium, sodium and water metabolism of isolated mitochondria. Protamine (4 mg/100 ml) induced swelling in rat liver and kidney mitochondria and impaired the ability of these mitochondria to concentrate potassium. These actions appeared to be associated with the uncoupling of oxidative phosphorylation. Protamine was without effect on the mitochondrial sodium concentration. Strophanthin at extremely high concentrations (1 gm/100 ml) was also found to induce swelling of rat liver, kidney and heart mitochondria and to interfere with the ability of the mitochondria to concentrate potassium. There was a tendency for mitochondrial sodium concentration to be elevated. It is concluded that the actions of protamine and strophanthin on mitochondria are qualitatively and quantitatively different from the actions of these substances on intact cells and that there are basic differences between the potassium concentrating mechanisms in mitochondria and in intact cells.

scholarly journals Peroxidative damage of mitochondrial respiration is substrate-dependent

2009 ◽  
pp. 685-692
Author(s):  
R Endlicher ◽  
P Křiváková ◽  
H Rauchová ◽  
H Nůsková ◽  
Z Červinková ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Rat Liver Mitochondria ◽  
Succinate Oxidation ◽  
Peroxidative Damage ◽  
Palmitoyl Carnitine ◽  
Low Concentrations ◽  
Tert Butyl Hydroperoxide ◽  
Strong Inhibitory Effect

The concentration-dependence of tert-butyl hydroperoxide (BHP) inhibitory effect on oxygen consumption in isolated rat liver mitochondria was measured in the presence of various respiratory substrates. Strong inhibitory effect at low concentrations of BHP (15-30 µM) was found for oxoglutarate and palmitoyl carnitine oxidation. Pyruvate and glutamate oxidation was inhibited at higher concentrations of BHP (100-200 µM). Succinate oxidation was not affected even at 3.3 mM BHP. Determination of mitochondrial membrane potential has shown that in the presence of NADH-dependent substrates the membrane potential was dissipated by BHP but was completely restored after addition of succinate. Our data thus indicate that beside peroxidative damage of complex I also various mitochondrial NADH-dependent dehydrogenases are inhibited, but to a different extent and with different kinetics. Our data also show that succinate could be an important nutritional substrate protecting hepatocytes during peroxidative damage.

scholarly journals Two forms of aspartate aminotransferase in rat liver and kidney mitochondria

1968 ◽  
Vol 108 (4) ◽  
pp. 619-624 ◽  
Author(s):  
M. M. Bhargava ◽  
A. Sreenivasan
Keyword(s):  
Rat Liver ◽  
Aspartate Aminotransferase ◽  
High Speed ◽  
Rat Kidney ◽  
Liver Mitochondria ◽  
Supernatant Fraction ◽  
Rat Liver Mitochondria ◽  
Aminotransferase Activity ◽  
Kidney Mitochondria ◽  
Liver And Kidney

1. Butan-1-ol solubilizes that portion of rat liver mitochondrial aspartate aminotransferase (EC 2.6.1.1) that cannot be solubilized by ultrasonics and other treatments. 2. A difference in electrophoretic mobilities, chromatographic behaviour and solubility characteristics between the enzymes solubilized by ultrasonic treatment and by butan-1-ol was observed, suggesting the occurrence of two forms of this enzyme in rat liver mitochondria. 3. Half the aspartate aminotransferase activity of rat kidney homogenate was present in a high-speed supernatant fraction, the remainder being in the mitochondria. 4. A considerable increase in aspartate aminotransferase activity was observed when kidney mitochondrial suspensions were treated with ultrasonics or detergents. 5. All the activity after maximum activation was recoverable in the supernatant after centrifugation at 105000g for 1hr. 6. The electrophoretic mobility of the kidney mitochondrial enzyme was cathodic and that of the supernatant enzyme anodic. 7. Cortisone administration increased the activities of both mitochondrial and supernatant aspartate aminotransferases of liver, but only that of the supernatant enzyme of kidney.

Effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and iodide on the thyrotropin-releasing hormone-induced thyrotropin release from superfused rat pituitary fragments

1991 ◽  
Vol 125 (4) ◽  
pp. 427-434 ◽  
Author(s):  
I. Szaboles ◽  
H. Schultheiss ◽  
H. Astier ◽  
F. A. Horster
Keyword(s):  
Potassium Iodide ◽  
Inhibitory Effect ◽  
Thyrotropin Releasing Hormone ◽  
Detectable Effect ◽  
Releasing Hormone ◽  
Iopanoic Acid ◽  
Rat Pituitary ◽  
High Concentrations

Abstract. The effects of triiodothyronine, triiodothyroacetic acid, iopanoic acid and potassium iodide were investigated on basal and stimulated thyrotropin release in an in vitro experimental model. Rat pituitary fragments were superfused by Medium-199 with or without T3 (10−7 mol/l), triiodothyroacetic acid (10−8-10−6 mol/l), iopanoic acid (10−7-10−5 mol/l) or potassium iodide (10−7-10−4 mol/l). This was followed by a 6-min pulse of thyrotropin-releasing hormone (10−8 mol/l). TSH was measured in 3-min fractions. The TRH-induced TSH release from the pituitary fragments was inhibited by T3 (10−7 mol/l), by triiodothyroacetic acid (10−7-10−6 mol/l), and by high concentrations of iodide (10−4 or 10−5 mol/l). Iopanoic acid had no significant effect at the concentrations tested. It is assumed that in vitro, and at similar concentrations, the inhibitory effect of triiodothyroacetic acid on the TRH-induced TSH secretion is comparable to that of T3, whereas iopanoic acid may have no direct detectable effect. In contrast, a direct inhibitory effect of inorganic iodide, at least in pharmacological concentrations in vivo, cannot be excluded.

scholarly journals The inhibition of pyruvate and ls(+)-isocitrate oxidation by succinate oxidation in rat liver mitochondria

1969 ◽  
Vol 114 (3) ◽  
pp. 589-596 ◽  
Author(s):  
T. König ◽  
D. G. Nicholls ◽  
P. B. Garland
Keyword(s):  
Cytochrome B ◽  
Rat Liver ◽  
Rat Heart ◽  
Fold Increase ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
The Other ◽  
Rat Liver Mitochondria ◽  
Succinate Oxidation ◽  
Rapid Flow

1. The effects of succinate oxidation on pyruvate and also isocitrate oxidation by rat liver mitochondria were studied. 2. Succinate oxidation was without effect on pyruvate and isocitrate oxidation when respiration was maximally activated with ADP. 3. When respiration was partially inhibited by atractylate, succinate oxidation severely inhibited the oxidation of pyruvate and isocitrate. 4. This inhibitory effect of succinate was associated with a two- to three-fold increase in the reduction of mitochondrial NAD+ but no change in the reduction of cytochrome b. 5. It is concluded that, in the partially energy-controlled state, respiration is more severely inhibited at the first phosphorylating site than at the other two. 6. The effects of succinate oxidation are compared with those of palmitoylcarnitine oxidation. It is concluded that a rapid flow of electrons directly into the respiratory chain at the level of cytochrome b is in itself inadequate to inhibit the oxidation of intramitochondrial NADH. 7. The effects of succinate oxidation on pyruvate oxidation were similar in rat heart and liver mitochondria.

Mitochondrial Bioenergetics after Nine-Day Treatment Regimen with Benzonidazole in Rats

2007 ◽  
Vol 26 (6) ◽  
pp. 571-575 ◽  
Author(s):  
D. A. Rendon
Keyword(s):  
Treatment Regimen ◽  
Day Treatment ◽  
Respiratory Control ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Sprague Dawley ◽  
Mitochondrial Energy Metabolism ◽  
Kidney Mitochondria ◽  
Mitochondrial Atp Synthase ◽  
Liver And Kidney

The bioenergetics of cardiac, liver, and kidney mitochondria after 9-day treatment regimen with benzonidazole was studied in rats. The drug was given by oral gavage to adult male Sprague-Dawley rats for 9 consecutive days (100 mg benzonidazole/kg body weight as daily dose). The assayed mitochondrial bioenergetic parameters were the state 4, state 3, respiratory control, efficiency of oxidative phosphorylation, and the activity of the mitochondrial ATP synthase. The results showed that mitochondrial parameters were not altered statistically after in cardiac and kidney mitochondria, but respiratory control in liver mitochondria was statistically increased with benzonidazole treatment. This change was likely due to a slight decrease in state 4 bioenergy metabolism. These results indicate that 9-day benzonidazole treatment regimen had no negative effect on cardiac, liver, and kidney mitochondrial energy metabolism but increased respiratory control in rat liver mitochondria.

ADP secretion and subsequent P2Y12 receptor signalling play a crucial role in thrombin-induced ERK2 activation in human platelets

2004 ◽  
Vol 92 (07) ◽  
pp. 114-123 ◽  
Author(s):  
Knut Fälker ◽  
Danica Lange ◽  
Peter Presek
Keyword(s):  
Platelet Aggregation ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
P2y12 Receptor ◽  
Detectable Effect ◽  
Receptor Signalling ◽  
Cellular Signal ◽  
Adp Receptor ◽  
High Concentrations ◽  
Erk2 Activation

SummaryStimulating human platelets with thrombin induces the activation of the extra cellular signal-regulated kinase 2 (ERK2). We demonstrate that this effect is highly dependent on ADP secretion and P2Y12 receptor signalling. AR-C69931MX (10 µM), a specific antagonist of the Gi-coupled P2Y12 ADP receptor, inhibits ERK2 activation induced by thrombin. Antagonists of the Gq-coupled P2Y1 ADP receptor, A3P5P (500 µM) and MRS2179 (100 µM), have no effect. ADP and its more potent analogue 2-methylthio-ADP alone (both up to 100 µM) do not induce ERK2 activation. Furthermore, we show that the inhibitory effect of AR-C69931MX on ERK2 activation induced by 0.1 U/ml thrombin as well as on platelet aggregation can be bypassed by epinephrine (1 and 10 µM), whereas epinephrine alone has no effect. Epinephrine acts on platelets mainly via α2A-adrenergic receptors, which, like P2Y12 receptors, couple to inhibitory G proteins. In addition, 2-methylthioADP as well as epinephrine provoke ERK2 activation at a thrombin concentration that alone has no detectable effect (0.05 U/ml). Thromboxane A2 (TXA2), which, like ADP, is released by activated platelets, acts as a positive feedback mediator. Stimulating the Gq-coupled TXA2-receptor with U46619 (10 µM), which leads to ADP secretion and P2Y12 receptor dependent platelet aggregation, also induces P2Y12-related ERK2 activation. The inhibition of U46619-induced ERK2 activation and platelet aggregation by AR-C69931MX are also rescued by epinephrine. Pretreatment with aspirin inhibits ERK2 activation induced by 0.1 U/ml thrombin, but has no effect at high concentrations of thrombin. The combination of U46619 and thrombin, at concentrations which alone have no effect, provokes ERK2 activation, suggesting that thrombin and released TXA2 act synergistically. Our data indicate that both primary signalling through Gq, which evokes ADP secretion, as well as subsequent coupling via Gi by the P2Y12 receptor are required for ERK2 activation.

scholarly journals Intermediates in fatty acid oxidation

1973 ◽  
Vol 132 (1) ◽  
pp. 61-76 ◽  
Author(s):  
H. B. Stewart ◽  
P. K. Tubbs ◽  
K. K. Stanley
Keyword(s):  
Liver Mitochondria ◽  
Fatty Acyl ◽  
Acid Oxidation ◽  
Aqueous Extracts ◽  
Multienzyme Complex ◽  
Acetyl Coa ◽  
Kidney Mitochondria ◽  
Liver And Kidney ◽  
Phenazine Methosulphate ◽  
Derivatives Of

1. Aqueous extracts of acetone-dried liver and kidney mitochondria, supplemented with NAD+, CoA and phenazine methosulphate, efficiently convert fatty-acyl-CoA compounds into acetyl-CoA; the process was followed with an O2 electrode. 2. Label from [1-14C]octanoyl-CoA appears in acetyl-CoA more rapidly than that from [8-14C]octanoyl-CoA. 3. Oxidation of [8-14C]octanoyl-CoA was terminated by addition of neutral ethanolic hydroxylamine and the resulting hydroxamates were separated chromatographically. Hydroxamate derivatives of 3-hydroxyoctanoyl-, hexanoyl-, butyryl- and acetyl-CoA were obtained. 4. These and other observations suggest that oxidation of octanoyl-CoA by extracts involves participation of free intermediates rather than uninterrupted complete degradation of individual molecules to acetyl-CoA by a multienzyme complex. 5. Intact liver mitochondria studied by the hydroxamate technique were also shown to form intermediates during oxidation of labelled octanoates. In addition to octanoylhydroxamate, [8-14C]octanoate gave rise to small amounts of hexanoyl-, butyryl- and 3-hydroxyoctanoyl-hydroxamate. In contrast with extracts, however, where the quantity of intermediates found was a significant fraction of the precursors, mitochondria oxidizing octanoate contained much larger quantities of octanoyl-CoA than of any other intermediate.

scholarly journals Phenethylbiguanide and the inhibition of hepatic gluconeogenesis in the guinea pig

1974 ◽  
Vol 144 (1) ◽  
pp. 49-57 ◽  
Author(s):  
Korechika Ogata ◽  
Mireille Jomain-Baum ◽  
Richard W. Hanson
Keyword(s):  
Guinea Pig ◽  
Rat Liver ◽  
Time Course ◽  
Liver Mitochondria ◽  
Inhibitory Effect ◽  
Progressive Increase ◽  
Rat Liver Mitochondria ◽  
Pig Liver ◽  
High Concentrations ◽  
Guinea Pig Liver

1. Phenethylbiguanide inhibits the synthesis of phosphoenolpyruvate from malate or 2-oxoglutarate by isolated guinea-pig liver mitochondria. This inhibition is time- and concentration-dependent, with the maximum decrease in the rate of phosphoenolpyruvate synthesis (80%) evident after 10min of incubation with 1mm-phenethylbiguanide. 2. The phosphorylation of ADP by these mitochondria is also inhibited at increasing concentrations of phenethylbiguanide and there is a progressive increase in AMP formation. Guinea-pig liver mitochondria are more sensitive to this inhibition in oxidative phosphorylation caused by phenethylbiguanide than are rat liver mitochondria. 3. Simultaneous measurements of O2 consumption and ADP phosphorylation with guinea-pig liver mitochondria oxidizing malate plus glutamate in State 3 indicated that phenethylbiguanide at low concentrations (0.1mm) inhibits respiration at Site 1. At higher phenethylbiguanide concentrations Site 2 is also inhibited. 4. Gluconeogenesis from lactate, pyruvate, alanine and glycerol by isolated perfused guinea-pig liver is inhibited to various degrees by phenethylbiguanide. Alanine is the most sensitive to inhibition (60% inhibition of the maximum rate by 0.1mm-phenethylbiguanide), whereas glycerol is relatively insensitive (25% inhibition at 4mm). 5. Gluconeogenesis from lactate and pyruvate by perfused rat liver was also inhibited by phenethylbiguanide, but only at high concentrations (8mm). Unlike guinea-pig liver, the inhibitory effect of phenethylbiguanide on rat liver was reversible after the termination of phenethylbiguanide infusion. 6. The time-course of inhibition of gluconeogenesis from the various substrates used in this study indicated a time-dependency which was related in part to the concentration of infused phenethylbiguanidine. This time-course closely paralleled that noted for the inhibition by phenethylbiguanide of phosphoenolpyruvate synthesis in isolated guinea-pig liver mitochondria.

Sign in / Sign up

Export Citation Format

Share Document