Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.9.3.1 (cytochrome oxidase)
 8,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A short review is given with respect to the status quo of the knowledge of mitochondrial protein synthesis in mammalian tissues. The inhibitory effects of antibiotic such as chloramphenicol and thiamphenicol are discussed from the point of possible complications for cardiac metabolism. It is shown that a decrease of the activity of cytochrome c oxidase, the terminal enzyme of the respiratory chain, caused an increase in the production of lactate, if beating heart cells are cultured in the presence of chloramphenicol. In vivo treatment of rabbits with the chloramphenicol analogue thiamphenicol causes a strong fall in the cytochrome aa3 content of the hearts. The results are discussed in the light of the possible implications for cardiac function and metabolism in man.
Acta Cardiol 1976
PMID:Protein synthesis in heart mitochondria: mechanism and metabolic aspects. 13 34

Male rats, aged 17 weeks at the end of experiments, were divided into four groups. Two groups lived in normal cage conditions with or without extra load (20% of the body weight) and two groups were trained by running with or without extra load for 8 weeks. Oxidation rates of succinate, glutamate + malate, palmitoylcarnitine, and pyruvate, and the activities of lactate dehydrogenase, citrate synthase, isocitrate dehydrogenase and cytochrome oxidase were measured in homogenates of the right ventricle and in those of the subendocardial and subepicardial layers of the left ventricle. Oxidation rates of succinate and palmitoylcarnitine tended to be higher in the subendocardium than in the subepicardium of sedentary control animals (p less than 0.1 and p less than 0.05, respectively). Transmural differences of succinate and palmitoylcarnitine oxidation rates were even more clear after running training (p less than 0.01 and p less than 0.05, respectively), after carrying extra load (p less than 0.001 and p less than 0.001, respectively) and after training carrying extra load (p less than 0.001 and p less than 0.05, respectively). Training also enhanced pyruvate oxidation rate in the subendocardium. Oxidation rates of all substrates were lower in the right ventricle than in the left ventricle. In control animals there were no regional differences in the myocardial enzyme activities and the training- or extra-load-induced changes were modest compared with the changes in the oxidation rates. The most significant change was the training-induced enhancement in the lactate dehydrogenase activity of the subendocardium (p less than 0.001 vs subepicardium). These results show greater subendocardial than subepicardial oxidation rates of certain substrates in the normal heart. These results also suggest that the myocardium adapts to increased work by increasing the subendocardial oxidation rate of some but not all substrates, indicating further that there may be qualitative mitochondrial differences in the different regions of the heart.
Basic Res Cardiol
PMID:Regional differences of substrate oxidation capacity in rat hearts: effects of extra load and endurance training. 207 98

The effects of endotoxemia on basic cardiovascular function were examined in the in situ hearts of five anesthetized rhesus monkeys. Cardiovascular function was assessed by each heart's ability to maintain sufficient oxygen delivery, as measured by the reduction-oxidation state of cytochrome aa3 during periods of increased work and decreased oxygen availability. In addition, the effects of endotoxemia on the baroreflex loop were tested by infusion of the alpha-agonist phenylephrine (5 micrograms/kg). Finally, the oxidative capacity of heart mitochondria, isolated 4 h after the infusion of endotoxin, was determined. Immediately following the 30 min intravenous infusion of endotoxin (10 mg/kg), there was a reduction of cytochrome aa3 evident in the paced heart (200 beats/min) exposed to a brief hypoxic episode. This reduction indicates a loss of the ability of the heart to adjust oxygen delivery to the metabolic needs of the subepicardium. The pressor response to phenylephrine was also affected immediately following infusion, decreasing to 14.5 +/- 9.2% of control at 4 h. The chronotropic response to phenylephrine, mediated by the baroreceptor reflex, was reduced at t = 30 mins and was essentially abolished 3 h after infusion. There was no diminution of the oxidative capacity of the isolated mitochondria. These data indicate that endotoxemia has early depressive effects on the cardiovascular system in nonhuman primates.
Can J Cardiol 1990 Apr
PMID:Early myocardial dysfunction induced with endotoxin in rhesus monkeys. 216 Mar 9

Functional and structural alterations of myocardial mitochondria were investigated after four conditions of myocardial ischaemia in guinea pig heart: (1) 45 min complete ischaemia, (2) 60 min low-flow anoxic perfusion (0.3 ml/g wet weight per minute) with a modified Tyrode solution, (3) as (2) with 0.4 mM palmitic acid added to the perfusate, and (4) as (2) with 0.4 mM oleic acid added. Under conditions (1) and (2) the loss of tissue ATP (20-30% of aerobic control) and the degree of mitochondrial injury were similar. But when fatty acids were present during low-flow anoxia, ATP loss and mitochondrial injury were more severe. Oleic acid caused greater injury than palmitic acid. The extent of mitochondrial injury corresponded to variations in mitochondrial long-chain acyl CoA content. Compared to aerobic control values, acyl CoA was increased 1.5 fold under condition (1), not significantly altered under condition (2), increased 3.2 fold under condition (3) and increased 4.3 fold under condition (4). In low-flow anoxia fatty acids enhanced the depression of oxidative phosphorylation, the loss of cytochromes, the inhibition of adenine nucleotide translocase and the reduction of mitochondrial Ca2+ sequestration. Fatty acid induced injury differed in quality from that of conditions (1) and (2): complex II dependent respiration was markedly affected, cytochrome b was lost extensively, and cytochrome oxidase activity was distinctly reduced. The results indicate that fatty acids, when administered to ischaemic myocardium, interfere with mitochondrial membranes at several sites, probably by their CoA esters. The more lipophilic oleyl moiety has a greater effect than the palmityl moiety.
Basic Res Cardiol 1987
PMID:Detrimental actions of endogenous fatty acids and their derivatives. A study of ischaemic mitochondrial injury. 282 81

The harbor seal (Phoca vitulina) is capable of protracted dives resulting in low arterial PO2 levels. The mammalian heart is an aerobic organ depending primarily on mitochondrial oxidations for energy (ATP). Heart mitochondria were isolated from freshly killed seals and the functional data obtained compared to dog heart mitochondria isolated under similar conditions. The percentage yields of mitochondria based on cytochrome oxidase recovery were essentially the same from dog and seal hearts. However, the actual quantity of mitochondrial protein obtained per gram of seal heart tissue was lower than that isolated from dog heart. Phosphorylating rates of respiration (State 3; Q02) and cytochrome content were significantly lower in seal heart mitochondria compared to dog. The data indicate that seal hearts have fewer mitochondria per gram of tissue, lower active respiratory rates and lower cytochrome contents than dog heart.
J Mol Cell Cardiol 1983 Jan
PMID:Comparative functional properties of mitochondria from seal and dog hearts. 630 93

Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
J Mol Cell Cardiol 1983 Oct
PMID:Production of free radicals and lipid peroxides in early experimental myocardial ischemia. 631 60

Histochemical alterations of acute and chronic doxorubicin (DOX) cardiotoxicity in the mouse were assessed by the localization of succinate dehydrogenase (SDH), coenzyme Q10 (CoQ), cytochrome oxidase (COX), creatine phosphokinase (CPK), lactate dehydrogenase (LDH), reduced glutathione (GSH), and intracellular calcium. Isolated myocytes intensely stained for calcium were found at 72 and 120 h under the acute protocol; altered staining patterns of SDH, CoQ, and COX, were evident at 120 h. Chronically, two patterns of intracellular calcium staining were evident: (1) intensely stained myocytes as found in the acute protocol; and (2) multiple discrete intracellular deposits suggestive of mitochondrial localization. Altered staining patterns of SDH, CoQ, COX, CPK, and LDH under the chronic protocol were only seen after abnormal staining was evident in trichrome stained sections. The presence of characteristic vacuolated myocardial cells in both acute and chronic protocols was confirmed by one micron epon-embedded toluidine blue stained sections and electron microscopy. These histochemical findings suggest that DOX alters the functional integrity of mitochondrial respiratory chain enzymes in the myocardial cell.
J Mol Cell Cardiol 1983 Aug
PMID:Histochemical alterations of acute and chronic doxorubicin cardiotoxicity. 667 10

Insulin increases the synthesis of mitochondrial proteins in the isolated perfused heart and total cell protein synthesis in neonatal cardiac myocytes. Since carnitine-dependent fatty acid oxidation is modulated by insulin in a variety of tissues, the effects of 1.7 microM insulin on the mitochondrial enzyme(s), carnitine palmitoyltransferase (malonyl-CoA-sensitive CPT-I and the matrix-facing CPT-II), were studied in neonatal rat cardiac myocytes cultured in the absence of serum. Following incubation in serum-free medium, there is a four-fold increase in the I50 of CPT-I for malonyl-CoA (3.8 microM) compared to cells cultured in serum-free medium to which insulin has been added (I50 = 0.8 microM). CPT-I activity in the insulin-supplemented, serum-free cultures is 57% higher (P < 0.002) than CPT-I activity in cells cultured in the absence of insulin; CPT-II activity is also significantly increased (P < 0.01) in the presence of insulin. Since CPT-II is an inner membrane protein, the CPT response to insulin may be coordinately regulated with other mitochondrial activities. Similar to CPT, cytochrome oxidase activity of cardiac myocytes in serum-free medium is increased 33% by insulin. Consistent with this finding, both CPT-II and cytochrome oxidase mRNA expression is elevated over control in the presence of insulin. CPT-II activity increases significantly only at very high insulin concentrations (1.7 microM), suggesting a role for insulin-like growth factor pathway. When myocytes are cultured in the presence of 1.7 microM insulin and then transferred to an insulin-free medium, subsequent addition of insulin does not stimulate uptake of deoxyglucose. These results suggest that the response of CPT to insulin is mediated by insulin-like growth factor activity and not by cellular glucose availability. The response of CPT to insulin does not appear to be mediated by the protein kinase C pathway since CPT-II activity is not reduced by the protein kinase C inhibitor, chelerythrine. Insulin significantly increases protein synthesis in the neonatal cardiac myocyte and in isolated mitochondria by increasing incorporation of labelled amino acid into total myocyte and/or mitochondrial protein. The degradation rate of radiolabelled protein in cardiac myocytes cultured in the presence of insulin is not different from that of insulin-deprived cells. The data suggest that insulin can affect the activity and expression of mitochondrial proteins, e.g., CPT, through the insulin-like growth factor-I pathway in neonatal cardiac myocytes.
J Mol Cell Cardiol 1995 Jan
PMID:Insulin-associated changes in carnitine palmitoyltransferase in cultured neonatal rat cardiac myocytes. 776 Mar 80

The effects of chronic embryonic ethanol exposure were evaluated in chick ventricular muscle. Ethanol treatments were administered on embryonic days 11, 13, 15, and 17 and chicks were sacrificed at various time points following treatments. Fluctuations in embryonic blood ethanol levels were examined following treatments. Developmental increases in the activities of mitochondrial enzymes, cytochrome oxidase (CO) and citrate synthase (CS), were observed. Ethanol exposure resulted in a depression in CO activity, but not CS activity. Since, a maximal depression in CO activity was seen with ethanol treatments of 75 mg/100 g, this dosing paradigm was adopted for subsequent experiments. A tissue-specific effect of ethanol was demonstrated as CO activity was unchanged in atrial, liver, pectoralis, and brain tissues. The role of mitochondrial DNA replication and transcription during the developmental up-regulation and ethanol-induced down-regulation of CO activity was evaluated using a cDNA probe for cytochrome oxidase subunit III (COIII). The relative levels of COIII mRNA and mitochondrial DNA (cpm/mg protein) decreased by 3-fold and 4-fold, respectively, across the developmental time course, while CO activity increased by 3.5-fold. Therefore, increases in mitochondrial DNA and mitochondrial mRNA transcripts are unlikely to be responsible for the developmentally-regulated increases in CO activity. Similarly, embryonic ethanol exposure failed to elicit alterations in COIII mRNA levels, indicating that the ethanol-induced depression in CO activity was not transcriptionally regulated. However, ventricular mitochondrial DNA concentrations were elevated in ethanol-treated embryos, indicating that ethanol-exposure either directly or indirectly induces mitochondrial DNA replication.
J Mol Cell Cardiol 1993 Feb
PMID:Ventricular mitochondrial gene expression during development and following embryonic ethanol exposure. 838 53

For the precise examination of the optical characteristics of cerebral tissue, we prepared hemoglobin-free perfused rat heads, from which trace amounts of blood were completely removed. In this preparation at 30 degrees C, the redox responses of the cytochrome oxidase components, heme a + a3 and copper, were followed spectrophotometrically in visible and near-infrared regions, and were correlated with the changes in neural activity as monitored by electroencephalography (EEG). During the aerobic-anaerobic transition, there was clear dissociation of the time courses of the reduction of heme a + a3 and copper; the reduction of heme a + a3 preceded the reduction of copper. The EEG activity decreased earlier than the reduction of heme a + a3. Pentylenetetrazole administration in normoxia caused the partial reduction of heme a + a3 but not of copper. The redox behaviors of cytochrome oxidase components in the brain were identical to those observed in isolated mitochondria. The usefulness of brain preparation for bridging the in vivo and in vitro studies is documented where various circulatory parameters could be controlled artificially.
 ...
PMID:Optical characterization of heme a + a3 and copper of cytochrome oxidase in blood-free perfused rat brain. 970 Jun 85


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