Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.99.3 (diaphorase)
5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of injected Photofrin II, a preparation enriched in hydrophobic dihaematoporphyrin ethers and esters, to photosensitize selected mitochondrial and cytosolic enzymes during illumination in vitro was examined. Preparations of R3230AC mammary tumours, obtained at designated times after a single dose of Photofrin II, displayed a time-dependent photosensitivity. Maximum inhibition of mitochondrial enzymes occurred at 24 hours post-treatment, whereas no inhibition of the cytosolic enzyme, pyruvate kinase, was observed over the 168 hour time course. At the selected 24 hour time point, mitochondrial enzyme photosensitisation was found to be drug dose (5.25 mg kg-1 Photofrin II) and light dose dependent, the rank order of inhibition being cytochrome c oxidase greater than F0F1 ATPase greater than succinate dehydrogenase greater than NADH dehydrogenase. We conclude that porphyrin species contained in Photofrin II accumulate in mitochondria of tumour cells in vivo and produce maximum photosensitisation at 24-72 hours after administration to tumour-bearing animals. The time course observed here with Photofrin II is similar to that seen previously with the more heterogenous haematoporphyrin derivative preparation in this in vivo-in vitro model.
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PMID:In vitro photosensitization of tumour cell enzymes by photofrin II administered in vivo. 254 13

This study was designed to elucidate harmful effects of acetylcholine on myocardial mitochondrial electron transport activity. Rats were cervically dislocated 3 h and 6 h after oral administration of pyridostigmine, an acetylcholinesterase inhibitor. The myocardial mitochondrial electron-transport activity (NADH-cytochrome c reductase, succinate-cytochrome c reductase and cytochrome c oxidase), and myocardial acetylcholine and norepinephrine concentrations were measured. Activities of cytochrome c oxidase were significantly decreased in the pyridostigmine-3h and the pyridostigmine-6h groups compared with untreated rats. Activity of NADH-cytochrome c reductase was significantly decreased 6 h after administration. No significant changes were observed in those of succinate-cytochrome c reductase among all groups. Pyridostigmine increased significantly myocardial acetylcholine concentration, however, no significant changes of myocardial norepinephrine concentrations were observed among all groups. It is indicated that these mitochondrial injuries might be dependent on an increase in acetylcholine level and independent of norepinephrine.
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PMID:Changes in myocardial mitochondrial electron transport activity in rats administered with acetylcholinesterase inhibitor. 255 31

The adverse effects of denopamine (TA-064) were investigated on rat myocardium in comparison with those of isoprenaline (isoproterenol). Experiment 1. Rats were treated with isoprenaline (10 mg/kg) or denopamine (10 mg/kg) once by subcutaneous injection. 15 h after drug administration, rat hearts were isolated, and heart mitochondria were prepared. Activities of three portions of electron transport chain (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) of mitochondria were measured. In rats treated with isoprenaline, significant decreases in NADH-cytochrome c reductase and cytochrome c oxidase activities were observed. While, in rats treated with denopamine, NADH-cytochrome c reductase activity was not decreased significantly, and decrease in cytochrome c oxidase activity was less than that observed in the isoprenaline group. Experiment 2. Rats were treated with isoprenaline (10 mg/kg) or denopamine (10 mg/kg) by subcutaneous injection once a day for 6 successive days. After the last drug administration, hearts were isolated, and cardiac membranes were prepared. Numbers of beta-adrenergic receptors were measured using 3H-dihydroalprenolol. In rats treated with isoprenaline, a significant decrease in the number of beta-adrenergic receptors was observed. On the contrary, administration of denopamine did not affect significantly the number of beta-adrenergic receptors.
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PMID:Effects of denopamine on rat myocardium in comparison with isoprenaline. 255 39

The Fe3(+)-doxorubicin complex undergoes reactions that suggest that the complex self-reduces to a ferrous oxidized-doxorubicin free radical species. The Fe3(+)-doxorubicin system is observed to reduce ferricytochrome c, consume O2 and react with 2,2'-bipyridine. Bipyridine acts as a "ferrous ion scavenger" as it reacts with the ferrous ion produced by Fe3(+)-doxorubicin self-reduction. In the absence of O2, a ferrous doxorubicin complex accumulates. In the presence of oxygen, Fe2+ recycles back to Fe3+. The rates of these reactions were measured and the Fe3(+)-doxorubicin self-reduction was determined to be the rate-determining step. The Fe3(+)-doxorubicin induced inactivation of cytochrome c oxidase and NADH cytochrome c reductase on beef heart submitochondrial particles occurs at a rate similar to Fe3(+)-doxorubicin self-reduction. Thus the rate at which damage to these mitochondrial enzymes occurs may be controlled by a nonenzymatic Fe3(+)-doxorubicin self-reduction.
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PMID:Self-reduction of the iron(III)-doxorubicin complex. 255 81

Ragged-red fibers (RRFs) are mainly seen in mitochondrial myopathy and related to biochemical defects in electron transfer chain on some occasions. Recently, some papers reported the occurrence of RRFs in the biopsied muscle of myotonic dystrophy (MyD). To examine whether the mitochondrial function is disturbed in MyD, we have studied the biopsied muscles of 12 cases with MyD (10 males and 2 females averaging 38 years of age) morphologically and mainly biochemically. RRFs, ranging from 2--20% of the muscle fibers, were identified in 5 out of 12 cases. On electron microscopy, these fibers had aggregated abnormally enlarged mitochondria with dene bodies, concentrically whirled membranous cristae and paracrystalline inclusions. Clinically, 4 of 5 cases with RRFs had mild to moderate and only 2 of 7 without RRFs had ophthalmoplegia. Bicycle ergometer exercise test showed abnormal increase of lactate/pyruvate ratio in three cases with RRFs. Histochemically, cytochrome c oxidase (CCO) activity was absent selectively in all of the RRFs. Immunohistochemical staining showed the presence of CCO protein by using monoclonal antibody which was specific to CCO subunit IV. Biochemical study with crude muscle extract of 11 cases of MyD showed decreases in NADH dehydrogenase, NADH CoQ reductase, succinate CoQ reductase (SCR), CCO, carnitine actyl transferase activities in most of cases regardless RRFs. To avoid the influence possibly derived from the various stages of muscle degeneration in the biopsied specimens, we calculated the ratio of the enzyme activities compared with succinate dehydrogenase which was located in the electron transfer chain and did not show any statistical difference regardless of RRFs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A study of mitochondrial electron transfer chain in myotonic dystrophy]. 259 36

The inhibitory effects of pure galloylglucose (1,2,3,4,6-penta-O-galloyl-beta-D-glucose) on the respiratory chain of rat liver mitochondria were investigated. The respiratory control ratio (RCR) decreased by 50% on addition of 20 microM pentagalloylglucose to highly coupled mitochondria, but the adenosine-5'-diphosphate/oxygen (ADP/O) ratio decreased only slightly. The RCR disappeared and the ADP/O ratio could not be measured at concentrations of pentagalloylglucose above 30 microM. On the other hand, the uncoupler-induced oxygen consumption was also inhibited. These findings suggest that pentagalloylglucose at low concentrations inhibits the electron transport system to decrease the RCR, but scarcely impairs the membrane, practically retaining the coupled reaction, while at high concentrations it impairs the structural integrity of the mitochondrial membrane. Pentagalloylglucose competitively inhibited succinate dehydrogenase activity, and noncompetitively inhibited reduced nicotinamide adenine dinucleotide (NADH) dehydrogenase and ubiquinol-1 oxidase activities of submitochondrial particles (SMP). However, it did not show significant inhibition of the cytochrome c oxidase activity of SMP. It is thus concluded that pentagalloylglucose, which is the lowest-molecular-weight component of tannic acid, exerts its effect on mitochondrial respiration and oxidative phosphorylation through action on the membrane and on succinate dehydrogenase, NADH dehydrogenase and cytochrome bc1 complex of mitochondria.
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PMID:The effects of 1,2,3,4,6-penta-O-galloyl-beta-D-glucose on rat liver mitochondrial respiration. 263 Jan

To explore the possibility of liver enzyme induction by deltamethrin, subacute intoxication was carried out in rats for 28 days, by administration 7.2 mg.Kg-1.day-1 of deltamethrin i.p. delivered by an osmotic pump inserted in the peritoneal cavity. The body weight curve of the treated rats increased slightly but not significantly compared to the controls. No neurotoxic effect was observed. Blood parameters were unchanged, except for eosinophilia and an increase in the plasma Na+ level. Cytochrome P-450, cytochrome b5, NADPH-cytochrome c reductase, esterases and the activities of six mixed function oxidases were assayed. No variation was noted. Ultrastructural study of the liver, more specially in midlobular region, showed that deltamethrin increased the number of mitochondria and altered their shape which became irregular. These findings were consistent with morphometric results. Succinate cytochrome c reductase, citrate synthase and cytochrome c oxidase were essayed, only this last showed a significant enhancement in deltamethrin treated rats.
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PMID:Effects on rats of subacute intoxication with deltamethrin via an osmotic pump. 263 42

The quinonoid anthracycline, doxorubicin (Adriamycin) is a potent anti-neoplastic agent whose clinical use is limited by severe cardiotoxicity. Mitochondrial damage is a major component of this cardiotoxicity, and rival oxidative and non-oxidative mechanisms for inactivation of the electron transport chain have been proposed. Using bovine heart submitochondrial preparations (SMP) we have now found that both oxidative and non-oxidative mechanisms occur in vitro, depending solely on the concentration of doxorubicin employed. Redox cycling of doxorubicin by Complex I of the respiratory chain (which generates doxorubicin semiquinone radicals, O2-, H2O2, and .OH) caused a 70% decrease in the Vmax. for NADH dehydrogenase during 15 min incubation of SMP, and an 80% decrease in NADH oxidase activity after 2 h incubation. This inactivation required only 25-50 microM-doxorubicin and represents true oxidative damage, since both NADH (for doxorubicin redox cycling) and oxygen were obligatory participants. The damage appears localized between the NADH dehydrogenase flavin (site of doxorubicin reduction) and iron-sulphur centre N-1. Succinate dehydrogenase, succinate oxidase, and cytochrome c oxidase activities were strongly inhibited by higher doxorubicin concentrations, but this phenomenon did not involve doxorubicin redox cycling (no NADH or oxygen requirement). Doxorubicin concentrations of 0.5 mM were required for 50% decreases in these activities, except for cytochrome c oxidase which was only 30% inhibited following incubation with even 1.0 mM-doxorubicin. Our results indicate that low concentrations of doxorubicin (50 microM or less) can catalyse a site-specific oxidative damage to the NADH oxidation pathway. In contrast, ten-fold higher doxorubicin concentrations (or more) are required for non-oxidative inactivation of the electron transport chain; probably via binding to cardiolipin and/or generalized membrane chaotropic effects. The development of agents to block doxorubicin toxicity in vivo will clearly require detailed clinical studies of doxorubicin uptake in the heart.
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PMID:Oxidative and non-oxidative mechanisms in the inactivation of cardiac mitochondrial electron transport chain components by doxorubicin. 271 42

Although acetylcholine is known to be involved in the genesis of skeletal muscle disturbance, its effect on cardiac muscle has been scarcely studied. In the present paper, using pyridostigmine, a cholinesterase inhibitor, the possible role of acetylcholine in the genesis of cardiomyopathy was investigated. In a mortality study, it was shown that pyridostigmine (100 mg/kg) caused death of 9/10 rats within 8 h, and that the lethality of such a dose could be significantly diminished by the subsequent administration of a total dose of 4 mg/kg atropine. In all other experiments, rats were divided into three groups; the control, untreated group; the pyridostigmine + atropine group in which atropine (2 mg/kg) was administered 5 min after pyridostigmine (60 mg/kg) administration; and the pyridostigmine group in which pyridostigmine (60 mg/kg) was administered orally. Rats were killed 3 h after pyridostigmine administration, and hearts were isolated. Heart mitochondrial electron transport activity (NADH-cytochrome c reductase, succinate-cytochrome c reductase, and cytochrome c oxidase) were measured enzymatically, and mitochondrial respiratory rates and control indices were measured polarographically. Structural changes in cardiac muscles of each group were observed by electron microscopy of cardiac sections. Acetylcholine levels of left ventricle were measured by high performance liquid chromatography. Activities of NADH-cytochrome c reductase and succinate-cytochrome c reductase were not affected by pyridostigmine administration; however, cytochrome c oxidase activity was significantly reduced in the pyridostigmine group. Atropine markedly lessened this reduction in activity. A protective effect of atropine was also observed morphologically. A protective effect of atropine was also observed morphologically. In the pyridostigmine group and the pyridostigmine + atropine group, left ventricular acetylcholine levels were increased significantly compared with the control.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of acetylcholine in pyridostigmine-induced myocardial injury: possible involvement of parasympathetic nervous system in the genesis of cardiomyopathy. 273 Mar 38

The stoichoimetry of vectorial H+ ejection coupled to electron flow through the cytochrome c oxidase (EC 1.9.3.1) of rat liver mitochondria was determined by a new rate/pulse method. This is a modification of the oxygen-pulse method. Electron flow through the oxidase is initiated by adding oxygen to suspensions of anaerobic mitochondria at a known and constant rate. Cytochrome c oxidase was examined directly or in combination with cytochrome c reductase (ubiquinol:ferricytochrome c oxidoreductase). In both cases the----H0+/2e- ratio was found to be constant during the time-course of oxygen reduction, and thus independent of delta pH. The stoichiometries observed were consistent with mechanistic stoichiometries of 2 and 6 for cytochrome c oxidase alone and cytochrome c oxidase together with cytochrome c reductase, respectively. The stoichiometry of cytochrome c reductase alone was also examined, by using ferricyanide in place of oxygen. The results obtained were consistent with the accepted mechanistic stoichiometry of 4 for this enzyme.
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PMID:Protonmotive stoichiometry of rat liver cytochrome c oxidase: determination by a new rate/pulse method. 282 93


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