Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Following symmetrical bilateral infusion of D-glucose into the basal ventromedial hypothalamus (BVMH), using Alzet minipumps (1 microliter/h of 10% D-glucose for 6 days), average daily food intake was reduced by 27% for the period of treatment. Symmetrical bilateral infusions into the posterior medial hypothalamus had a transitory effect on feeding, as did asymmetrical and unilateral infusions. Infusion of L-glucose into the BVMH did not yield a chronic reduction in food intake. Included in the infused solutions were tracer amounts of [14C]glucose, [14C]proline or [14C]leucine to permit radioautographic estimations of infusate dispersal in the brain and axonal transport patterns from the infusion sites. Infusions were generally well-restricted to 1-1.5 mm of the cannulae tips, and descending transport of amino acids was highest in substantia nigra and midline structures of the mesencephalon and pons including central gray, ventral tegmental area, raphe and ventral tegmental nuclei. These results provide evidence for an energy intake regulatory mechanism situated in the BVMH whose outputs may modulate activity in the substantia nigra and midline brain stem areas.
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PMID:D-glucose infusions into the basal ventromedial hypothalamus and feeding. 617 Dec 96

bI1 RNA (excised from the first intron of the long form of the cytochrome b gene of Saccharomyces cerevisiae mitochondria) hybridizes with the two strands of a Bg/II-MboI DNA segment from this region. This fraction is resistant to digestions by DNase I and RNase T1 and disappears completely upon alkali hydrolysis. Strand-specific labeling of an intronic DNA fragment, cloned in pBR322 plasmid, was accomplished through the use of a T4 DNA polymerase. The purity of the probes was demonstrated by cloning an exon-intron fragment and labeling it by the same procedure; mRNA and pre-mRNA bands hybridized only with the transcribed DNA strand whereas bI1 RNA hybridized with the two strands under the stringent washing conditions employed (tm + 20 degrees C). Several experimental results argue against the possibility that the observation of two complementary bI1 RNA strands results from a partial self-complementarity of the RNA. A pre-mRNA intermediate from a box8 (G5046) mutant, still containing this intron, hybridizes only with the transcribed DNA strand of the pure intronic probe. The amount of the non-sense bI1 RNA strand is very low, in cells from two wild-type strains, relative to the sense RNA strand during the early stages of growth on glucose. It increases as the cells are released from glucose repression. bI1 RNA is resistant to RNase. Very little self-complementarity is seen by computer analysis of the sequence. Purified bI1 RNA is seen by electron microscopy under non-denaturing conditions as a mixture of double-stranded circular and linear molecules thus confirming the existence of the two complementary strands. The disappearance of all material following alkali hydrolysis demonstrates that these are indeed two RNA strands. Under fully denaturing conditions a mixture of single-stranded circular and linear molecules is seen as reported previously (Cell, 19, 321-329, 1980). We conclude that yeast mitochondria contain the two complementary bI1 RNA strands, one circular and the other linear. Considering a largely asymmetrical transcription of the mitochondrial genome in yeast and assuming that circularization of some intronic RNAs is part of RNA processing, we do not believe that the two strands are each a mixture of linear and circular molecules. The ratio of non-sense to sense bI1 RNA in a cytoplasmic petite mutant, A1B1, also varies according to growth conditions.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Yeast mitochondria contain a linear RNA strand complementary to the circular intronic bI1 RNA of cytochrome b. 620 24

Research in detecting regional changes in brain metabolism related to functional activity is reviewed and supplemented by original results from positron emission tomography (PET) and the 18F-fluorodeoxyglucose method (FDG). A formula for calculating the value of local cerebral glucose metabolism (LCMRGlc) is discussed. Results concerning auditory stimulation suggest that metabolic responses are determined by the stimulus content and analysis strategy used by the subject rather than the side of stimulation. Tactile stimulation of the hand and fingers caused asymmetrical increases in LCMRGlc confirming topographic maps of the postcentral gyrus and other functional studies. Data from visually stimulated normal subjects show how the visual hemifields project to the opposite calcarine cortex. Studies of patients with hemianopsia or various field defects demonstrated that metabolic scanning can reveal alterations of cortical function not detectable by CT scan. Data obtained reveal the ability of metabolic mapping to subdivide the occipital cortex into distinct regions. Such measurements may also anticipate the course of visual recovery. Findings of increased overall right-hemispheric metabolism during the performance of verbal and spatial cognitive tasks are consistent with earlier results from right-handed males. Results for the frontal eye fields provide the first experimental evidence that lateralized metabolic activity, produced by cognitive tasks, causes similarly lateralized activity within a motor region. It is further demonstrated that FDG is able to provide information on such states as vigilance and anxiety.
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PMID:Positron emission tomographic studies of sensory stimuli, cognitive processes and anxiety. 660 51

The bidirectional fluxes and energetics of methotrexate transport in Ehrlich ascites tumor cells were profoundly altered in a high [K+], low [Na+] buffer (K+ buffer). Incubation of cells for 30 min in K+ buffer reduced influx by 27% and the efflux rate constant by 53%. This asymmetrical inhibition of bidirectional fluxes increased the net exchangeable intracellular methotrexate level per cell, but the actual intracellular methotrexate concentration at the steady state was similar to that in Na+ buffer, since the high [K+] caused an increase in intracellular water. Because cells exposed to K+ buffer were depolarized, the apparent electrochemical potential difference for methotrexate was markedly reduced. However, the steady-state intracellular methotrexate level was still related to the extracellular concentration by an absorption isotherm, indicating asymmetry in the bidirectional fluxes similar to that observed in Na+ buffer and thus predicting that transmembrane gradients would be produced at very low extracellular methotrexate concentrations. Glucose, which had little effect on bidirectional fluxes and reduced the steady-state level of methotrexate in Na+ buffer, stimulated influx, inhibited efflux and rapidly increased the steady state in K+ buffer similar to the effects of glucose in the presence of glucose in the presence of iodoacetate in Na+ buffer. Finally, cells exposed to k+ buffer exhibited trans-stimulation of [3H]methotrexate influx when loaded with non-labeled methotrexate, a phenomenon not observed in Na+ buffer. The results indicate that although methotrexate transport is not affected by transient changes in the cationic composition of the extracellular compartment, prolonged exposure of cells to a high [K+], low [Na+] environment markedly alters the physical properties of the cells and the transport parameters for methotrexdate and reveals characteristics of the methotrexate carrier system that are not evident in other buffer systems.
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PMID:K+-induced alterations of energetics and exchange diffusion in the carrier-mediated transport of the folic acid analog, methotrexate, in Ehrlich ascites tumor cells. 719 70

Pig kidney cell line LLC-PK1 cultured on a collagen-coated membrane filter formed a continuous sheet of oriented asymmetrical epithelial cells joined by circumferential occluding junctions. In the presence of 5.5 mM D-glucose, a potential difference (PD) of 2.8 mV, apical bath negative, short-circuit current Isc of 13.2 microA . cm-2, and transepithelial resistance of 211 omega . cm2 were recorded. Isc and PD were reduced by phlorizin added to the apical bath but were unaffected when phlorizin was placed in the basolateral bath. Ouabain or the replacement of Na by tris-(hydroxymethyl)aminomethane or choline abolished the Isc. The sugar concentrations required to produce the half-maximal Isc were 0.13 mM beta-methyl-D-glucoside, 0.28 mM D-glucose, 0.65 mM alpha-methyl-D-glucoside, 0.77 mM 6-deoxy-D-glucose, 4.8 mM D-galactose, and 29 mM 3-O-methylglucose. When [Na] was reduced, the D-glucose required for half-maximal SCC increased. Isotopically 3H- and 14C-labeled D-glucose were used to determine simultaneous bidirectional fluxes; a resultant net apical-to-basolateral flux was present and could be abolished by phlorizin. The transported isotope cochromatographed with labeled D-glucose, indicating negligible metabolism. The cell culture model provides advantages for investigation of mechanisms of transepithelial glucose transport.
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PMID:Transepithelial glucose transport in cell culture. 721 56

Relationships between subcellular adenine nucleotides (ATP, ASP), heart function and oxidative myocardial metabolism were studied in the isolated working guinea pig heart. The heart preparations were stimulated by noradrenaline and utilized pyruvate alone or in combination with glucose as energy-providing substrates. Using density gradient centrifugation of lyophilized myocardial homogenates in non-aqueous media the following subcellular distribution of ATP and ADP, respectively, was obtained: The concentration of ATP in the cytosol was higher than in the mitochondria while the content of ADP was not different. The overall ATP/ADP ratio in the cytosol was more than 10-fold lower than the concentration ratio of free ATP and ADP in the cytosol as derived from the cytosolic creatine kinase equilibrium. Furthermore, the mitochondrial ATP/ADP ratio was much lower than the free cytosolic ATP/ADP ratio. The concentration term of the phosphorylation potential of ATP (RT in [ADP] x [Pi]/[ATP]) was thus higher in the cytosol than in the mitochondria. Myocardial function and substrate oxidation exhibited typical augmentations during infusion of 0.08 microM noradrenaline. However, increased heart performance and oxidative myocardial metabolism were not associated with major changes in the cytosolic ATP or ADP contents. On the other hand, the free ATP/ADP ratio and particularly the phosphorylation state of ATP, i.e. the ration [ATP]/[ADP] x [Pi], were decreased in the cytosol. In contrast, in the mitochondria adenine-nucleotide concentration ratios were not substantially changed under the same conditions. The results are compatible with an asymmetrical translocation of adenine nucleotides across the mitochondrial membrane in working hearts. The reciprocal relationship between rates of oxidative metabolism and free cytosolic ATP/ADP ratio indicates that mitochondrial respiration in the intact heart could be controlled by the phosphorylation state of the extramitochondrial ATP.
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PMID:Compartmentation of adenine nucleotides in the isolated working guinea pig heart stimulated by noradrenaline. 721 67

The pig kidney cell line LLC-PK1 cultured on a collagen coated membrane filter formed a continuous sheet of oriented asymmetrical epithelial cells joined by occluding junctions. A transepithelial electrical potential (PD) and short-circuit current (SCC) were dependent on the presence of Na and sugar in the apical bathing solution. In the presence of 5.5 mM D-glucose, a PD of 2.8 mV. apical surface negative a SCC of 13 microA cm-2 and transepithelial resistance of 211 ohm.cm2 were recorded. The SCC was promptly reduced by the addition of phlorizin to the apical bath but unaffected when placed in the basolateral bath. The effect on SCC of various sugars was compared by the concentrations required for half-maximal SCC: 0.13 mM beta-methyl-D-glucoside, 0.28 mM D-glucose, 0.65 mM alpha-methyl-D-glucoside, 0.77 mM 6-deoxy-D-glucose, 4.8 mM D-galactose, and 29 mM 3-O-methyl-glucose. When [Na] was reduced, the concentration of D-glucose required for half-maximal SCC increase. Isotopically labeled 3H and 14C D-glucose were used to simultaneously determine bidirectional fluxes; a resultant net apical-to-basolateral transport was present and abolished by phlorizin. The transported isotope cochromatographed with labeled D-glucose, indicating negligible metabolism of transported glucose. The pig kidney cell line, LLC-PK1, provides a cell culture model for the investigation of mechanisms of transepithelial glucose transport.
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PMID:Transepithelial transport in cell culture: D-glucose transport by a pig kidney cell line (LLC-PK1). 724 72

Rats having hypothalamic electrodes that elicited gnawing, eating, and drinking in free-moving tests received intermittent electrical stimulation for 45 min following i.v. injection of [14C] deoxyglucose. Autoradiographs of regional brain glucose utilization were made by the method of Sokoloff et al. ('77). To maximize the detectability of first-order neuronal effects and minimize potentially complex transsynaptic effects, baseline metabolism and synaptic transmission were reduced by light barbiturate anesthesia. Laterally asymmetrical increases in glucose utilization indicative of elicited activity were largely coterminous with the known projections of the lateral hypothalamus and some projections of adjoining areas, indicating that most first-order efferents were above threshold for deoxyglucose visualization, while most transsynaptic effects were subthreshold. Although the majority of hypothalamic projections were similarly affected in control rats that received hypothalamic stimulation that elicited other responses, a number were activated significantly less than in the rats whose electrodes induced gnawing, eating, and drinking. Chief among these areas was a continuous descending pathway from the ventral tegmental area through the lateral tegmentum to the cuneiform and parabrachial nuclei. Smaller and/or less reliable increases above controls were found in the dorsomedial caudate-putamen, the posterolateral zona incerta, the anterior lateral central gray, the caudal linear nucleus, the laterodorsal tegmental nucleus, the pontine tegmental nucleus, and a previously undescribed pathway lying medially between the pontine medial lemniscus and cerebral peduncle. These areas, especially the lateral tegmental and parabrachial zone, are the most likely candidates for the pathways and/or destinations of the directly excited efferents or fibers of passage that constitute the first link in the elicitation of gnawing, eating, and drinking by lateral hypothalamic stimulation. Since self-stimulation and exploratory activity were elicited by control as well as experimental electrodes, they are probably dependent on other projections among those affected similarly in both groups.
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PMID:[14C]Deoxyglucose mapping of first-order projections activated by stimulation of lateral hypothalamic sites eliciting gnawing, eating, and drinking in rats. 745 85

The dynamic properties of the glucose/glucose-6-phosphate cycle are studied under conditions where the phosphatase and kinase interconverting enzymes are spatially distributed. A semi-artificial membrane made of compacted plant cell walls bearing active phosphatase in its natural state, separates two compartments, one of these compartments containing soluble hexokinase. Depending only upon the two enzyme activity levels and the initial distribution of the substrates, numerous asymmetrical and vectorial behaviours can be observed, such as facilitated glucose 6-phosphate diffusion, active transport of either glucose or glucose 6-phosphate and sequential (alternative) transport between glucose and glucose 6-phosphate. A diffusion-partition reaction coupling can account for these oriented mass transfers. The possibility of such a coupling in this model system is clearly dictated by the global analog of the Curie principle. These results may provide new insight on (a) the still obscure role played by the cell-wall phosphatase activities, particularly their involvement in the transport of exogenous phosphomonoesters, and (b) the actual in vivo operation of substrate and protein cycles in view of the heterogeneity and anisotropy of the cellular milieu.
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PMID:Various vectorial behaviours of a spatially structured substrate cycle. 805 73

This paper reports on the detailed morphology of inferior olivary neurons in the cat following electrophysiological examination, intracellular injection with horseradish peroxidase, and gamma aminobutyric acid (GABA) immunocytochemistry. The activity of olivary cells was recorded intracellularly in vivo and their response to mesodiencephalic stimulation was tested. In a number of cases their response to stimulation of the contralateral superior cerebellar peduncle was also tested. Mesodiencephalic stimulation resulted in monosynaptic, and superior peduncle stimulation in disynaptic activation of cells in the medial accessory and principal olivary subdivisions. Rebound olivary activity was usually only found after mesodiencephalic stimulation. Light microscopic investigation of osmicated and Araldite embedded Vibratome sections was facilitated considerably when performing the osmication in a glucose solution. Peroxidase labeled olivary cells, like that earlier described for Golgi-impregnated material, possess a complex globular dendritic geometry. Especially, and unlike Golgi material, the abundance of exceptionally long and complex spiny appendages could be appreciated. The axons usually stemmed from first order dendrites and did not give rise to recurrent axon collaterals. The ultrastructural analysis of this material, mainly from serial sections, was combined with postembedding GABA immunohistochemistry. In this way, GABAergic as well as non-GABAergic profiles were studied in conjunction with HRP labeled cellular elements. The GABAergic terminals usually contained pleomorphic vesicles and made symmetrical synapses whereas non-GABAergic terminals nearly always formed asymmetrical synapses and contained round or oval vesicles. Most, if not all, HRP labeled spiny appendages were incorporated in glomeruli. A particular spiny appendage may contribute more than one spine head to a glomerular core, which, on average, consisted of spiny elements of six different neurons. A glomerular core is surrounded by approximately the same amounts of GABAergic and non-GABAergic boutons. Also, all spiny appendages, and most of their individual spine heads, are contacted by GABAergic as well as non-GABAergic boutons. Spiny appendages on the axon hillock may be incorporated in dendritic glomeruli, however, most synapses with the hillock were made by GABAergic boutons. The combined physiological and morphological observations imply that 1) the cerebellar nuclei can exert an excitatory influence on inferior olivary neurons through a mesodiencephalic relay, 2) the GABAergic nucleo-olivary input seems to be capable of diminishing the oscillatory tendencies of olivary neurons, and 3) the mesodiencephalic (non-GABAergic) and cerebellar (GABAergic) input may subserve a timing function since these inputs systematically impinge upon the same olivary spines.
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PMID:Electron microscopy of in vivo recorded and intracellularly injected inferior olivary neurons and their GABAergic innervation in the cat. 838 92


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