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

Intrastriatal transplantation of fetal striatal (STR), cortical (CTX), or ventral mesencephalic (VM) tissue into the normal striatum has been shown to produce behavioral deficits (38). Here, we have examined the cellular elements of the transplants and their connectivity with the host using histochemistry for cytochrome oxidase (CO) and acetylcholinesterase (AChE), immunocytochemistry for glial fibrillary acidic protein (GFAP), OX42, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), and cholecystokinin (CCK). Autoradiography for dopamine D1 and D2, muscarinic cholinergic, and serotonin 5-HT1 and 5-HT2 receptors at 5-15 months after transplantation was also investigated. CO staining showed that all transplants were metabolically active. The STR and VM transplants contained AChE-positive neurons and fibers. The CTX transplants exhibited AChE terminals with an appearance similar to that of the host cortex. AChE staining within the STR transplants was patchy. 5-HT-, TH-, and DBH-immunoreactive (IR) fibers were found in the STR and CTX transplants. In two of six CTX transplants, many TH-IR neurons were present. The VM transplants contained many TH-IR, 5-HT-IR, and DBH-IR cell bodies and fibers. CCK-IR stain was found in the VM transplant and was coextensive with regions containing TH-IR cell bodies. Fibers stained by all markers crossed the transplant and host border. Receptor autoradiography revealed that muscarinic cholinergic and 5-HT2 receptors were present in the STR, CTX, and VM transplants. In addition, dopamine D1 and D2 receptors were present in the STR transplants. Intermittent heavy staining for GFAP and OX42 were observed along the border of most transplants and the hosts. It was noted that high densities and hypertrophy of GFAP- or OX42-stained astrocytes or microglia, respectively, were present in the transplants and adjacent host. OX42-stained macrophages were found in many transplants. The present results indicate that intrastriatal transplants into the intact normal brain express numerous histochemical, immunocytochemical, and receptor features characteristic of the appropriate adult tissues. The afferents from the host extend into the STR and CTX transplants, and neural fibers from the VM transplants grew into surrounding host tissue, suggesting possible anatomical connection. Ultrastructural evidence is needed to determine if these fibers form synaptic connections. The results from GFAP and OX42 immunocytochemical staining support the possibility suggested by behavioral studies that damage to the host brain is induced by neural transplantation.
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PMID:Striatal, ventral mesencephalic and cortical transplants into the intact rat striatum: a neuroanatomical study. 165 Dec 54

This study examines possible changes in energy demands by developing neural crest cells in vitro using cytochrome oxidase (C.O.) histochemistry and immunohistochemical labeling of adrenergic (autonomic) cells and primary sensory neurons. Cytochrome oxidase is a key enzyme for oxidative metabolism and energy production, and it is used as a sensitive metabolic marker for neurons in the brain and dorsal root ganglia. In primary neural crest cell cultures, C.O. staining intensities differ among 4 distinct cellular populations (sensory neurons, adrenergic cells, pigment cells, and non-neuronal neural crest cells). At all stages, pigment cells exhibit extremely low C.O. staining. Neurons (both primary sensory and adrenergic cells) have higher C.O. activity than other cell types such as non-neuronal neural crest cells. This indicates that neurons have higher energy demands and presumably higher levels of functional activity than other cell types at least under the present culture conditions. All neurons in neural crest cell cultures elevate their energy demands during development, implying that energy metabolism and functional activity increase with neuronal maturation. At all stages, early determined sensory neurons exhibit more intense C.O. staining than late-developing sensory neurons. The difference in C.O. activity between the two populations of sensory neurons may be caused by different levels of functional activity due to their different time course of development. Tetrodotoxin (TTX) at 0.5-1 microM concentrations causes a decrease in the level of C.O. activity in the early determined sensory neurons, which may be correlated with a decrease in the functional activity of these neurons. Triple staining combining C.O. histochemistry with indirect immunofluorescence of antibodies against the stage specific embryonic antigen-1 (SSEA-1, which labels quail sensory neurons) and dopamine-beta-hydroxylase (DBH, which labels adrenergic cells) distinguish the level of C.O. activity between sensory neurons and autonomic cells. DBH+ cells exhibit relatively low C.O. staining. However, the C.O. activity among SSEA-1+ neurons varies from high to low levels. In general, SSEA-1+ sensory neurons are much more C.O. reactive than DBH+ autonomic cells. This suggests that developing sensory neurons in culture may have higher spontaneous and/or synaptic activity than autonomic neurons.
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PMID:Developing neural crest cells in culture: correlation of cytochrome oxidase activity with SSEA-1 and dopamine-beta-hydroxylase immunoreactivity. 198 90

Adrenal medullary chromaffin-vesicle membranes contain a transmembrane electron carrier that may provide reducing equivalents for intravesicular dopamine beta-hydroxylase in vivo. This electron transfer system can generate a membrane potential (inside positive) across resealed chromaffin-vesicle membranes (ghosts) by passing electrons from an internal electron donor to an external electron acceptor. Both ascorbic acid and isoascorbic acid are suitable electron donors. As an electron acceptor, ferricyanide elicits a transient increase in membrane potential at physiological temperatures. A stable membrane potential can be produced by coupling the chromaffin-vesicle electron-transfer system to cytochrome oxidase by using cytochrome c. The membrane potential is generated by transferring electrons from the internal electron donor to cytochrome c. Cytochrome c is then reoxidized by cytochrome oxidase. In this coupled system, the rate of electron transfer can be measured as the rate of oxygen consumption. The chromaffin-vesicle electron-transfer system reduces cytochrome c relatively slowly, but the rate is greatly accelerated by low concentrations of ferrocyanide. Accordingly, stable electron transfer dependent membrane potentials require cytochrome c, oxygen, and ferrocyanide. They are abolished by the cytochrome oxidase inhibitor cyanide. This membrane potential drives reserpine-sensitive norepinephrine transport, confirming the location of the electron-transfer system in the chromaffin-vesicle membrane. This also demonstrates the potential usefulness of the electron transfer driven membrane potential for studying energy-linked processes in this membrane.
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PMID:An electron transfer dependent membrane potential in chromaffin-vesicle ghosts. 298 56

The role of copper in maintaining normal neurological function has been examined in animals copper-deficient by dietary means, and in the genetic disorders of copper homeostasis -- Menkes' kinky-hair disease in humans and the mottled (Mo) mutants in the mouse. With the exception of the disorder in Mo mice, reduced myelination is a constant feature of these copper diseases but there is otherwise a lack of conformity in the structural defects produced in different species. Dietary copper-deficient animals show a reduction in noradrenaline and dopamine concentrations, together with a depressed tyrosine 3-monooxygenase activity (EC 1.14.16.2). Noradrenaline concentrations are also reduced in brain tissue of Mo mice and this reduction is associated with a decrease in the vivo activity of the copper metalloenzyme, dopamine beta-monooxygenase (EC 1.14.17.1). Many tissues contain potent inhibitors of dopamine beta-monooxygenase activity, and assays of this enzyme have utilized cupric ions to inactivate these inhibitors. The elevated in vitro activities of dopamine beta-monooxygenase obtained for both Mo brain and adrenal tissue may therefore reflect either a reduced inactivation of these endogenous inhibitors in the intact animal or the activation in vitro of apoenzyme. Concentrations of dopamine and tyrosine 3-monooxygenase are unchanged in Mo mice. The reduction in dopamine and tyrosine 3-monooxygenase activity in dietary copper-deficient animals may therefore reflect neuronal loss rather than reduced catalytic activity of the catecholamine biosynthetic pathway. The possible effects of depressed activities of cytochrome c oxidase (EC 1.9.3.1) and superoxide dismutase (EC 1.15.1.1) in the development of neurological dysfunction are also discussed, and attention is drawn to the possible significance of the elevated uptake of neutral amino acids, especially tyrosine and tryptophan, by Mo brain tissue.
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PMID:Copper and neurological function. 690 87

Male Holtzman rats were offered a semipurified low-copper (Cu) diet (0.36 mg Cu/kg) for 5-6 weeks to further characterize cardiac hypertrophy, which accompanies Cu deficiency. Cu-adequate (controls) were given supplemental Cu (20 micrograms/ml) in their drinking water, and Cu-deficient rats were given deionized water. Cu-deficient rats had lower plasma ceruloplasmin activity, lower hemoglobin levels, higher heart weights, and similar body weights compared with Cu-adequate rats. The relative degree of hypertrophy in the right ventricle of Cu-deficient rats was significantly higher (2.3-fold) than that in the left ventricle and atria (both were 1.9-fold higher than the values in Cu-adequate rats). Edema was not detected. Ventricles and atria of Cu-deficient rats had markedly lower Cu and no significant differences in iron concentrations compared with Cu-adequate rats. Heart protein concentrations were not altered consistently by Cu deficiency. Enzyme activities of the cuproenzymes cytochrome-c oxidase (CCO), copper, zinc-superoxide dismutase (SOD), dopamine beta-monooxygenase (DBM), peptidylglycine alpha-amidating monooxygenase (PAM), and the selenoenzyme glutathione peroxidase (GPX) were measured in the atria and ventricles. Cu deficiency resulted in lower specific activities of all cuproenzymes, with the exception of ventricular PAM. GPX was not altered by chamber region or diet. Specific activity of PAM was 200-fold higher in atria than in ventricles in control rats. Catecholamine analyses by HPLC confirmed that, like ventricular tissue, atria of Cu-deficient rats had lower noreplnephrine and higher dopamine concentrations, consistent with lower DBM activity. Another experiment detected no differences between the two dietary groups in mean arterial blood pressure, heart rates, or responses after challenge with anglotensin II, phenylepherine, or acetylocholine in cannulated rats. In this Cu-deficient rat model, all chambers of the heart exhibit similar and marked hypertrophy. Biochemical alterations following dietary Cu deficiency were also similar in atria and ventricles. The hypertrophic response appears different from the response to simple pressure or volume overload.
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PMID:Atria and ventricles of copper-deficient rats exhibit similar hypertrophy and similar altered biochemical characteristics. 927 Jul 21

Tissue fractionation was used as an analytical tool to study the subcellular distribution of an adenosine triphosphatase activated by Mg2+ in adrenal medullae of the pig and ox and in whole adrenals of the rat. By measuring adenosine triphosphatase and various enzymes in the fractions obtained by differential centrifugation, the distribution pattern of adenosine triphosphatase was found to differ markedly from that of markers like catecholamines, dopamine beta-hydroxylase or cytochrome oxidase. In the pig and ox the distribution of inosine diphosphatase paralleled that of adenosine triphosphatase. After equilibration through sucrose density gradients, no adenosine triphosphatase activity was detected in the chromaffin granules in the rat. However, in bovine adrenal medullae, a large part of the adenosine triphosphatase activity equilibrated in that area of the gradient in which the chromaffin granules were found. This adenosine triphosphatase distribution pattern was an artefact produced by applying a too concentrated sample to the gradient. When a more diluted sample of bovine tissue was used no adenosine triphosphatase activity was found to be associated with the chromaffin granules. The present results lead to a reconsideration of the role of the adenosine triphosphatase in some processes in which the chromaffin granules are involved. Moreover, the degree of purity of many chromaffin granule preparations is again questioned.
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PMID:Tissue fractionation and catecholamines--IV. Adenosine triphosphatase in chromaffin granules: a distribution artefact. 1137 Feb 33

The trace metal copper (Cu) plays an essential role in biology as a cofactor for many enzymes that include Cu, Zn superoxide dismutase, cytochrome oxidase, ceruloplasmin, lysyl oxidase, and dopamine beta-hydroxylase. Consequently, Cu transport at the cell surface and the delivery of Cu to intracellular compartments are critical events for a wide variety of biological processes. The components that orchestrate intracellular Cu trafficking and their roles in Cu homeostasis have been elucidated by the studies of model microorganisms and by the characterizations of molecular basis of Cu-related genetic diseases, including Menkes disease and Wilson disease. However, little is known about the mechanisms for Cu uptake at the plasma membrane and the consequences of defects in this process in mammals. Here, we show that the mouse Ctr1 gene encodes a component of the Cu transport machinery and that mice heterozygous for Ctr1 exhibit tissue-specific defects in copper accumulation and in the activities of copper-dependent enzymes. Mice completely deficient for Ctr1 exhibit profound growth and developmental defects and die in utero in mid-gestation. These results demonstrate a crucial role for Cu acquisition through the Ctr1 transporter for mammalian Cu homeostasis and embryonic development.
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PMID:Essential role for mammalian copper transporter Ctr1 in copper homeostasis and embryonic development. 1139 Oct 5

Menkes disease (MD) is a neurodegenerative disorder characterized by a copper deficiency in the brain. It is caused by the defective intestinal absorption of copper resulting from a deficiency of a copper-transporting ATPase, ATP7A. This gives rise to an accumulation of copper in the intestine. The copper deficiency in the brain of MD patients cannot be improved by copper injections, because the administered copper accumulates at the blood-brain barrier and is not transported across to the neurons. To resolve this problem, we investigated the effect of a combination therapy of copper and sodium diethyldithiocarbamate (DEDTC), a lypophilic chelator, in an animal model of MD, the macular mouse. Four-week-old macular mice treated with 50 mug of CuCl2 on the 7th day after birth were used. Experimental mice were given a subcutaneous injection of CuCl2 (4 microg) and an intraperitoneal injection of DEDTC (0.2 mg/g body weight) twice a week for 4 weeks and then sacrificed. Copper concentrations and cytochrome-c oxidase activity in the brains of treated mice were higher than those of control macular mice, which received only copper or saline. The ratios of brain noradrenaline to dopamine and of adrenaline to dopamine were also increased by the treatment, suggesting that the activity of dopamine beta-hydroxylase, a copper-dependent enzyme, was improved by the treatment. Liver and renal function tests showed no abnormalities in the treated mice, although copper concentrations in the kidneys of treated mice were higher than those of control macular mice. These results suggest that DEDTC facilitates the passage of copper across the blood-brain barrier and that the combination therapy of copper and DEDTC may be an effective treatment for the neurological disturbances suffered by patients with MD.
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PMID:Effect of copper and diethyldithiocarbamate combination therapy on the macular mouse, an animal model of Menkes disease. 1643 90