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)

Inorganic lead, added to the diet of suckling rat in high doses, produces an encephalopathy similar to that seen in the immature human. Pathologic changes of edema and hemorrhage are seen earliest and are most prominent in the cerebellum. In this study, we measured respiration in cerebral hemisphere and cerebellar mitochondria isolated from led-fed and age-matched normal rat pups. Lactating mothers were begun on ad libitum feedins containing 4% lead carbonate when their pups were 2 weeks old. Mitochondria were isolated by differential centrifugation. Oxygen consumption was measured polarographically, NAD-linked respiration was measured with oxidation of the substrate pair, glutamate and malate. Cytochrome oxidase (cytochrome c oxidase, EC. 1.9.3.1) activity was measured in the presence of tetramethyl-p-phenylenediamine dihydrochloride (TMPD) and ascorbate. Within 2 days of starting lead feedings, rat pups showed a significant loss in body weight (P less than 0.02) and, after 1 week, a significant loss in cerebral hemisphere wet weight (P less than 0.01) compared with controls. Overt encephalopathy appeared in pups from two of nine litters receiving lead feedings for 1 week and in half of the litters after 2 weeks of feedings. None of the lead-fed mothers developed encephalopathic signs. With oxidation of the NAD-linked substrate pair, there was a progressive decrease, relative to controls, in ADP/O ratios in both cerebellar and cerebral mitochondria from lead-fed animals. After 2 weeks these differences were significant in mitochondria from both regions (cerebellum, P less than 0.02; cerebrum, P less than 0.005). Respiratory control ratios were significantly lower in cerebellar mitochondria from lead-fed rats within 2 days of beginning feedings (P less than 0.02) and in mitochondria from both regions after 2 weeks of lead feedings (cerebellum, P less than 0.01; cerebrum, P less than 0.05). The decrease in control ratios in cerebellar mitochondria from animals receivint lead feedings for 1 week or less was due to a small decrease in state 3 respiration and a large, but inconsistent, increase in state 4 respiration. The decrease in control ratios in both cerebellar and cerebral hemisphere mitochondria after 2 weeks of lead feedings was due to a marked inhibition of state 3 respiration, relative to controls (cerebellum, P less than 0.01; cerebral hemisphers, P less than 0.05). In cerebellar mitochondria from lead-fed animals, cytochrome oxidase activity showed similar changes compared with controls: a highly significant (P less than 0.001) increase within 2 days of beginning feedings and a significant (P less than 0.01) decrease after 2 weeks of feedings.
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PMID:Early effects of inorganic lead on immature rat brain mitochondrial respiration. 17 53

This study was undertaken to assess the effect of a calcium antagonist, nicardipine (N), added in a cardioplegic solution on the ischemic myocardium. Isolated rat hearts were perfused with oxygenated Krebs Ringer Bicarbonate (KRB) solution by Langendorff's perfusion method and were subjected to 2 hours of ischemic arrest at 30 degrees C with multidose cardioplegia (every 30 min, for 5 min) and a subsequent 60 min of reperfusion. HR, LVP, coronary flow and oxygen tension of coronary effluent were monitored. Oxygen saturation of intracellular myoglobin and redox state of mitochondrial cytochrome aa3 in the myocardial cell were continuously measured throughout studies by a spectrophotometer. Oxygenated crystalloid cardioplegic solution (KRB) containing 25 mM of potassium was used. 40 rats were divided into 4 groups (10 rats each) according to the concentration of N (none, 0.5, 1 and 2 mg/L) in fully oxygenated potassium cardioplegic solution (PO2: 601 +/- 31 mmHg). The percent recovery of pressure-rate product after reperfusion was compared in each group and the optimal concentration of N was found to be 1 mg per liter of cardioplegic solution. No significant difference was found between Group Ia (N = 0 mg/L) and Group Ib (N = 1 mg/L) in metabolic or hemodynamic recovery after reperfusion. In other experiments, 40 rats in Group IIa (N = 0 mg/L, n = 20) and Group IIb (N = 1 mg/L, n = 20) received 10 ml of poorly oxygenated cardioplegic solution (PO2: 215 +/- 10 mmHg) on each reinfusion followed by a 25 min interval of ischemic arrest. The index of oxygen utilization, MVO2/pressure-rate product after reperfusion was significantly lower in Group IIb than in Group IIa (p less than 0.05). The results show that the addition of N (1 mg/L) to the cardioplegic solution preserved a more aerobic state (higher intracellular oxygen level) in the myocardium by further suppressing myocardial oxygen demand during the ischemic period which resulted in better myocardial protection. Therefore, it is concluded that the addition of N to the cardioplegic solution enhances myocardial preservation during myocardial ischemia.
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PMID:[Functional and metabolic effects of nicardipine on ischemic rat hearts with multidose potassium cardioplegia]. 237 97

Rat kidney was studied histochemically and in electron microscope during administration of lithium carbonate for 14 days in doses of 4 mmol/l. Morphological examination demonstrated signs of damage exclusively to the epithelial cells in the proximal tubule. Histochemical examination demonstrated a major reduction of the reactions for succinate dehydrogenase and cytochrome oxidase. No difference was found in the intensity of the reaction for alkaline phosphatase and Ca-ATPase during lithium treatment as compared to controls. Additional observation demonstrated, only in histological examination, an increased number of cells of the macula densa.
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PMID:Ultrastructural and histochemical assessment of proximal renal tubule in rats during administration of lithium carbonate. 251 37

Purified epithelial basolateral membrane vesicles were prepared from lobster hepatopancreas by sorbitol gradient centrifugation. Na+-K+-adenosinetriphosphatase, alkaline phosphatase, and cytochrome-c oxidase enzyme activities in the final membrane preparation were enriched 9.6-, 1.4-, and 0.4-fold, respectively, compared with their activities in the original tissue homogenate. Vesicle osmotic reactivity was demonstrated using 60-min equilibrium 36Cl uptake experiments at a variety of transmembrane osmotic gradients. 36Cl uptake into vesicles preloaded with HCO3 was significantly greater than into vesicles lacking HCO3. This exchange process was stimulated by a transmembrane proton gradient (internal pH greater than external pH). Proton-gradient-dependent Cl-HCO3 exchange was potential sensitive and stimulated by an electrically negative vesicle interior. 36Cl influx (4-s exposures) into HCO3-loaded vesicles occurred by the combination of 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid sensitive, carrier-mediated transfer and "apparent diffusion." 36Cl influx was a hyperbolic function of both internal [HCO3] and internal [Cl]. The two internal anions displayed a 100-fold difference in apparent affinity constants with HCO3 being strongly preferred. 36Cl influx was stimulated more by preloaded monovalent than by divalent anions. Na was an inhibitor of proton-dependent anion antiport, whereas K had no effect. A model for HCl-HCO3 antiport is suggested that employs combined transmembrane concentration gradients of Cl and HCO3 to power anion exchange and transfer protons against a concentration gradient.
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PMID:Proton-stimulated Cl-HCO3 antiport by basolateral membrane vesicles of lobster hepatopancreas. 303 81

Oxa1p is a mitochondrial inner membrane protein that is mainly required for the insertion/assembly of complex IV and ATP synthase and is functionally conserved in yeasts, humans, and plants. We have isolated several independent suppressors that compensate for the absence of Oxa1p. Molecular cloning and sequencing reveal that the suppressor mutations (CYT1-1 to -6) correspond to amino acid substitutions that are all located in the membrane anchor of cytochrome c1 and decrease the hydrophobicity of this anchor. Cytochrome c1 is a catalytic subunit of complex III, but the CYT1-1 mutation does not seem to affect the electron transfer activity. The double-mutant cyt1-1,164, which has a drastically reduced electron transfer activity, still retains the suppressor activity. Altogether, these results suggest that the suppressor function of cytochrome c1 is independent of its electron transfer activity. In addition to the membrane-bound cytochrome c1, carbonate-extractable forms accumulate in all the suppressor strains. We propose that these carbonate-extractable forms of cytochrome c1 are responsible for the suppressor function by preventing the degradation of the respiratory complex subunits that occur in the absence of Oxa1p.
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PMID:Mutations in the membrane anchor of yeast cytochrome c1 compensate for the absence of Oxa1p and generate carbonate-extractable forms of cytochrome c1. 975 93

The CNS contains high levels of the glycosaminoglycan hyaluronan, and neural cells express a variety of proteins that are members of the hyaladherin family of hyaluronan-binding proteins. We have previously shown that the hyaladherin RHAMM (receptor for hyaluronan-mediated motility; CD168) is expressed by neural cells in culture; plays a role in astrocyte motility, neurite migration, and axonal growth; and is widely distributed in neurons and oligodendrocytes of developing and adult rat CNS. Here we demonstrate differential localization of various forms of RHAMM in subcellular fractions of adult rat brain. Western blotting indicated the presence of 66, 75, and 85-90 kDa molecular weight RHAMM forms in whole-brain homogenates. Subfractionation revealed enrichment of the 66 and 85-90 kDa forms in soluble fractions, whereas the 75 kDa form was enriched in mitochondrial fractions. This latter form was retained in osmotically shocked mitochondria, but was liberated by alkali carbonate, suggesting a nonintrinsic mitochondrial membrane association. By double immunohistochemical labeling for RHAMM and the mitochondrial marker cytochrome oxidase, RHAMM was localized to isolated mitochondria in vitro and to neuronal mitochondria in vivo. Hyaluronan-sepharose chromatography and cetylpiridinium chloride precipitation confirmed the hyaluronan-binding capacity of RHAMM forms. By calmodulin-affinity chromatography, endogenously expressed brain RHAMM was demonstrated to bind calmodulin in a Ca2+-dependent manner. These results, together with reports of RHAMM association with actin and microtubules in other systems, suggest a role of RHAMM in calmodulin-mediated cell signaling to cytoskeletal elements and/or mitochondria in the CNS and invoke novel functions of its interactions with hyaluronan.
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PMID:Subcellular distribution, calmodulin interaction, and mitochondrial association of the hyaluronan-binding protein RHAMM in rat brain. 1143 24

Experimental data show that elevation of intracellular pH leads to severe lesions of brain cells. Acidification of intracellular fluid by accumulation of lactate may compensate the effect of respiratory alkalosis. Increased serum pH, and low PCO2, associated with hyperlactataemia (sometimes incorrectly called 'acidosis') have been reported in children with Leigh syndrome (LS). The aim of the study was to determine whether respiratory alkalosis is characteristic of patients with LS due to SURF1 mutations. All venous blood gas data (88 samples) of 18 spontaneously breathing LS patients with recently established SURF1 mutations, hospitalized during 1986-2000, were retrospectively reviewed. The data of an affected boy who survived on a respirator for more than 3 months (79 daily samples) were analysed separately. In spontaneously breathing patients, the data indicated that the patients had compensated or partially compensated respiratory alkalosis (pH 7.388+/-0.060, Pco2 29.2+/-5.7 mmHg, HCO3- 17.4+/-3.0 mmol/L, BE -6.7+/-3.2 mmol/L). Bicarbonate excretion was detected in urine of two examined LS cases in spite of decreased serum HCO3-. In the affected child maintained on a respirator, simple manipulation of the inspired CO2 tension to establish a normal pressure of 35-45 mmHg automatically caused an increase of serum HCO3- concentration to a normal value of 26.3+/-2.9 mmol/L (and BE to +2.2+/-3.1 mmol/L), in spite of cytochrome oxidase (COX) deficiency due to a confirmed SURF1 mutation. We suggest that respiratory alkalosis (hypocapnia) of Leigh syndrome patients with SURF1 mutations results from compulsory hyperventilation and speculate that hypocapnia may contribute to Leigh-like brain damage in the SURF1-deficient patients as well as in other patients presenting with Leigh-like syndrome. The supposition that accumulation of lactate may protect the brain of LS patients from alkalosis-related damage requires further study. Avoidance of any factors stimulating hyperventilation of LS patients and caution when attempting to correct low plasma bicarbonate are suggested.
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PMID:Compulsory hyperventilation and hypocapnia of patients with Leigh syndrome associated with SURF1 gene mutations as a cause of low serum bicarbonates. 1180 7

1. The kinetics of the inactivation of photosynthesis by 2537 A in Chlorella pyrenoidosa and Scenedesmus D(1) indicate that, while the destruction process is largely a first order effect, higher order effects also occur, which become evident at low exposures. In agreement with previous observations, endogenous respiration is insensitive to exposures which inactivate photosynthesis. 2. In Scenedesmus D(1) a solid dose of ultraviolet has no more effect on the photosynthetic apparatus than a dose of equal total duration interrupted by periods of photosynthesis. Nor is any difference noted if the cells are in a different buffer, e.g. 0.05 M KH(2)PO(4), or carbonate-bicarbonate buffer 9. 3. In C. pyrenoidosa, a solid dose and an interrupted dose cause equal effects on photosynthesis when neutral phosphate buffer is used. If the ultraviolet exposure schedules are identical, equal effects are also noted in cells suspended in buffer 9, and in 0.05 M phosphate (pH 6.2). Solid exposures are, however, much more effective than interrupted exposures, when buffer 9 is used. 4. Oxygen evolution (Hill reaction), photosynthesis, and photoreduction in Scenedesmus D(1) are equally sensitive to a given dose of ultraviolet. The mechanism responsible for adaptation to hydrogen metabolism is not more sensitive to ultraviolet than is the photosynthetic mechanism. The O(2)/H(2)/CO(2) reaction in darkness is less sensitive to ultraviolet than any of the above reactions. 5. Glucose oxidation by C. pyrenoidosa, and colony formation in Scenedesmus D(1) are far more sensitive to a given dose of ultraviolet than photosynthesis in these organisms. 6. The photosynthetic apparatus of C. pyrenoidosa is more sensitive to ultraviolet than that of Scenedesmus D(1). 7. The Hill reaction in chloroplast fragments is also inactivated by 2537 A by a first order process. Exposures which inactivate this reaction completely have no effect on polyphenol oxidase, cytochrome oxidase, or catalase in the same chloroplast preparation. 8. After irradiation, the survival of photosynthesis in Scenedesmus D(1) and of the Hill reaction in chloroplast fragments are independent of the light intensity used to measure these processes. 9. No significant changes occur in the ultraviolet absorption of chloroplasts after an exposure to 2537 A, which completely inactivates the Hill reaction.
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PMID:Some effects of 2537 A on green algae and chloroplast preparations. 1483 43

A detailed nonlinear four-region (red blood cell, plasma, interstitial fluid, and parenchymal cell) axially distributed convection-diffusion-permeation-reaction-binding computational model is developed to study the simultaneous transport and exchange of oxygen (O2) and carbon dioxide (CO2) in the blood-tissue exchange system of the heart. Since the pH variation in blood and tissue influences the transport and exchange of O2 and CO2 (Bohr and Haldane effects), and since most CO2 is transported as HCO3(-) (bicarbonate) via the CO2 hydration (buffering) reaction, the transport and exchange of HCO3(-) and H+ are also simulated along with that of O2 and CO2. Furthermore, the model accounts for the competitive nonlinear binding of O2 and CO2 with the hemoglobin inside the red blood cells (nonlinear O2-CO2 interactions, Bohr and Haldane effects), and myoglobin-facilitated transport of O2 inside the parenchymal cells. The consumption of O2 through cytochrome-c oxidase reaction inside the parenchymal cells is based on Michaelis-Menten kinetics. The corresponding production of CO2 is determined by respiratory quotient (RQ), depending on the relative consumption of carbohydrate, protein, and fat. The model gives a physiologically realistic description of O2 transport and metabolism in the microcirculation of the heart. Furthermore, because model solutions for tracer transients and steady states can be computed highly efficiently, this model may be the preferred vehicle for routine data analysis where repetitive solutions and parameter optimization are required, as is the case in PET imaging for estimating myocardial O2 consumption.
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PMID:Simultaneous blood-tissue exchange of oxygen, carbon dioxide, bicarbonate, and hydrogen ion. 1677 61

In 1998, a unique subterranean ecosystem was discovered in numerous isolated calcrete (carbonate) aquifers in the arid Yilgarn region of Western Australia. Previous morphological and genetic analyses of a subterranean water beetle fauna suggest that calcrete aquifers are equivalent to closed island habitats that have been isolated for millions of years. We tested this hypothesis further by phylogeographic analyses of subterranean amphipods (Crangonyctoidea: Paramelitidae and Hyalidae) using mitochondrial DNA sequence data derived from the cytochrome oxidase I gene. Phylogenetic analyses and population genetic analyses (samova) provided strong evidence for the existence of at least 16 crangonyctoid and six hyalid divergent mitochondrial lineages, each restricted in their distribution to a single calcrete aquifer, in support of the 'subterranean island (archipelago) hypothesis' and extending its scope to include entirely water respiring invertebrates. Sequence divergence estimates between proximate calcrete populations suggest that calcretes have been isolated at least since the Pliocene, coinciding with a major aridity phase that led to the intermittent drying of surface water. The distribution of calcretes along palaeodrainage channels and on either side of drainage divides, have had less influence on the overall phylogeographic structure of populations, with evidence that ancestral crangonyctoid and hyalid species moved between catchments multiple times prior to their isolation within calcretes. At least two potential modes of evolution may account for the diversity of subterranean amphipod populations: dispersal/vicariance of stygobitic species or colonization of calcretes by surface species and independent evolution of stygobitic characteristics.
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PMID:Subterranean archipelago in the Australian arid zone: mitochondrial DNA phylogeography of amphipods from central Western Australia. 1739 Dec 74


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