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)

A study has been made with human red cells of sodium movements that are sensitive to the drug furosemide. The aim was to see if furosemide-sensitive movements that are symmetrical (exchange) became asymmetrical (net transport) on replacement of chloride with nitrate as the major external anion. Cells were incubated for 4 h at 37 degrees C with 140 mM sodium, and chloride or nitrate as the principal anion. Under a variety of conditions (presence and absence of ouabain or furosemide, or both) the cell sodium concentration was always higher when chloride was replaced with nitrate. The cells became leakier to sodium. Tracer studies indicated that, in contrast to the results in chloride medium, the decrease in sodium influx was greater than the fall in efflux when furosemide was added to cells in nitrate medium. The results confirm that the sensitivity of sodium efflux to furosemide depended on chloride. However, influx showed a different sensitivity in that furosemide still inhibited in cells incubated in nitrate medium. The stimulation of sodium influx with nitrate medium was independent of external potassium (10-50 mM) and the furosemide-sensitive influx was also constant. It is concluded that symmetrical transmembrane sodium movements with cells in chloride medium became downhill asymmetrical in nitrate medium, giving a net gain of cell sodium that was insensitive to ouabain and sensitive to furosemide. The drug thus partly retarded the gain of cell sodium that otherwise occurred in the somewhat leaky cells.
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PMID:The change from symmetry to asymmetry of a sodium transport system in red cell membranes. 285 58

The molecular properties of the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7 were investigated. The receptor was found to represent a highly asymmetrical molecule with a sedimentation coefficient, s20,w, of approximately 8 S, a Stokes radius of 7-8 nm, and a calculated Mr approximately equal to 260,000-300,000. In comparison, the Hepa 1c1c7 glucocorticoid receptor in analogy to the glucocorticoid receptor in general as well as the C57BL/6 mouse and rat hepatic dioxin receptors are molecules with an s20,w value of 4-5 S, a Stokes radius of approximately 6 nm, and a calculated Mr approximately equal to 100,000. In the presence of 20 mM sodium molybdate, a large Mr approximately equal to 270,000-310,000 form of the Hepa 1c1c7 glucocorticoid receptor is stabilized which is hydrodynamically indistinguishable from the Mr approximately equal to 260,000-300,000 Hepa 1c1c7 dioxin receptor. Sodium molybdate does not have any effect on the molecular properties of the Hepa 1c1c7 dioxin receptor. In conclusion, the large form of dioxin receptor present in Hepa 1c1c7 mouse hepatoma cells in the absence of sodium molybdate is strikingly similar to molybdate-stabilized steroid hormone receptors as well as the molybdate-stabilized form of the dioxin receptor previously demonstrated in rat hepatic cytosol. Therefore, the Hepa 1c1c7 dioxin receptor might offer an interesting model for studies on the structure and function of Mr approximately equal to 300,000 forms of soluble receptors.
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PMID:The receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in the mouse hepatoma cell line Hepa 1c1c7. A comparison with the glucocorticoid receptor and the mouse and rat hepatic dioxin receptors. 302 14

The interaction between membrane proteins and cytoplasmic structural proteins is thought to be one mechanism for maintaining the spatial order of proteins within functional domains on the plasma membrane. Such interactions have been characterized extensively in the human erythrocyte, where a dense, cytoplasmic matrix of proteins comprised mainly of spectrin and actin, is attached through a linker protein, ankyrin, to the anion transporter (Band 3). In several nonerythroid cell types, including neurons, exocrine cells and polarized epithelial cells homologues of ankyrin and spectrin (fodrin) are localized in specific membrane domains. Although these results suggest a functional linkage between ankyrin and fodrin and integral membrane proteins in the maintenance of membrane domains in nonerythroid cells, there has been little direct evidence of specific molecular interactions. Using a direct biological and chemical approach, we show here that ankyrin binds to the ubiquitous (Na+ + K+)ATPase, which has an asymmetrical distribution in polarized cells.
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PMID:Ankyrin binding to (Na+ + K+)ATPase and implications for the organization of membrane domains in polarized cells. 303 71

The urinary bladder epithelium in mammals, including humans, has a low permeability to ions and small molecules such as sodium, urea and water. Two structures, asymmetrical luminal plasma membrane and tight junction between superficial cells, have been said responsible for the urine-blood barrier. The permeability of junctional complex between superficial cells to lanthanum was observed in rat urinary bladder epithelium by transmission electron microscopy (TEM). In the normal bladder epithelium, confirmed by bacteriological examination, most junctions between superficial cells are the tight junctions and 1 to 9% of the junctions are leaky. The lanthanum, known to penetrate the leaky junctions, is demonstrated in the intercellular space between intermediate and basal cells. This suggests that desmosomes between these cells have no barrier function. In the experimentally inflammatory bladder epithelium all junctions are tight and no leaky junction is found between superficial cells. In contrast, if the superficial cells were stripped off in the inflammatory change, the lanthanum penetrates the junction between denuded intermediate cells. In the normal bladder epithelium the structural junctions between superficial cells have no changes during contraction and distension. Thus this suggests that the permeability to lanthanum does not change during contraction and distension.
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PMID:[Architectural ultrastructure of the urinary bladder epithelium. II. Changes in the urine-blood barrier in the contracted and distended state in the normal and inflammatory bladder]. 337 2

The physico-chemical properties of the dioxin and glucocorticoid receptors from rat liver and wild-type and mutant cell lines were investigated and compared. In rat liver, the receptors are virtually indistinguishable. Both are highly asymmetrical proteins with axial ratios of 12-15, have Stokes radii of 6 nm and sedimentation coefficients of approximately 4 S. This results in a calculated apparent mol. wt of approximately 100,000. The dioxin receptor from the mouse hepatoma cell line Hepa 1c1c7 represents an atypical form of the dioxin receptor with a pronounced tendency to aggregate to form Mr approximately equal to 300,000 complexes in high ionic strength and in the absence of sodium molybdate. In the presence of sulphydryl reducing agents, however, the Hepa 1c1c7 dioxin receptor dissociates to an Mr approximately 100,000 species. In analogy to the nt- mutant glucocorticoid receptor in mouse lymphoma cells, there is no gross change in the structure of the nt- dioxin mutant in mouse hepatoma cells compared with the wild-type receptor. The nt- dioxin receptor does, however, have a reduced affinity for DNA.
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PMID:The dioxin receptor: a comparison with the glucocorticoid receptor. 338 53

The crystal structure of a daunomycin-d(CGTACG) complex has been solved by X-ray diffraction analysis and refined to a final R factor of 0.175 at 1.2-A resolution. The crystals are in a tetragonal crystal system with space group P4(1)2(1)2 and cell dimensions of a = b = 27.86 A and c = 52.72 A. The self-complementary DNA forms a six base pair right-handed double helix with two daunomycin molecules intercalated in the d(CpG) sequences at either end of the helix. Daunomycin in the complex has a conformation different from that of daunomycin alone. The daunomycin aglycon chromophore is oriented at right angles to the long dimension of the DNA base pairs, and the cyclohexene ring A rests in the minor groove of the double helix. Substituents on this ring have hydrogen-bonding interactions to the base pairs above and below the intercalation site. O9 hydroxyl group of the daunomycin forms two hydrogen bonds with N3 and N2 of an adjacent guanine base. Two bridging water molecules between the drug and DNA stabilize the complex in the minor groove. In the major groove, a hydrated sodium ion is coordinated to N7 of the terminal guanine and the O4 and O5 of daunomycin with a distorted octahedral geometry. The amino sugar lies in the minor groove without bonding to the DNA. The DNA double helix is distorted with an asymmetrical rearrangement of the backbone conformation surrounding the intercalator drug. The sugar puckers are C1,C2'-endo, G2,C1'-endo, C11,C1'-endo, and G12,C3'-exo. Only the C1 residue has a normal anti-glycosyl torsion angle (chi = -154 degrees), while the other three residues are all in the high anti range (average chi = -86 degrees). This structure allows us to identify three principal functional components of anthracycline antibiotics: the intercalator (rings B-D), the anchoring functions associated with ring A, and the amino sugar. The structure-function relationships of daunomycin binding to DNA as well as other related anticancer drugs are discussed.
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PMID:Interactions between an anthracycline antibiotic and DNA: molecular structure of daunomycin complexed to d(CpGpTpApCpG) at 1.2-A resolution. 356 61

The theory of structural parallelism put forward by A. A. Zavarzin (Senior) has been supported by the analysis of cytological specificity of effector organs involved in water-salt homeostasis, and of the excretory system of vertebrates and invertebrates. The similarity in morphofunctional organization of different excretory organs (i.e. the presence of ultrafiltration apparatus and cells which make it possible to absorb all vitally important substances) is likely to result from the fact that the excretory organ should excrete not only the final products of metabolism, but also any exogenic substances in addition to those which although important, are excessive for the organism. The brush border of asymmetrical epithelial cells of excretory organs is presumably a morphological expression of the structure which accounts for the inward transport of all physiologically important substances. Specificity of the membrane mechanism of water and sodium transport accounts for the identical principles in the structure of cells and areas of cell contacts of epithelia in different organs involved in the formation of hypotonic (saliva glands, renal tubules) or hypertonic fluids (salt glands, marine teleost gills).
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PMID:[The physiological determinants of the parallelism (unity) of histological structures]. 371 74

The effects of chronic maternal salicylism on fetal growth were studied in chronically catheterized pregnant rabbits. Graded intravenous infusions of sodium salicylate were given continuously between days 22 and 29 of gestation. Maternal plasma salicylate concentrations (mean +/- SD) of 12.0 +/- 1.6 mg/dl (low-dose group) or 24.1 +/- 5.3 mg/dl (high-dose group) were achieved. Control rabbits were infused with saline solution. Pups were delivered by hysterotomy on day 29. Fetal/maternal salicylate concentration ratios were near unity for both infusion groups. There were significant dose-related reductions (mean +/- SD) in fetal weight (control, 39.7 +/- 6.7 gm; low-dose group, 34.4 +/- 6.4 gm; high-dose group, 22.2 +/- 7.1 gm; p less than 0.001) and in crown-rump length (control, 9.7 +/- 0.45 cm; low-dose group, 9.1 +/- 0.68 cm; high-dose group, 7.7 +/- 0.86 cm; p less than 0.001). There was a significant reduction in fetal brain weight only in the high-dose group, and brain weight/fetal weight ratios were increased, suggesting relative sparing of brain growth. Liver weight was significantly reduced in both low- and high-dose groups. In contrast to results in previous animal studies, standardized intravenous maternal salicylate administration in rabbits induced a reproducible and dose-dependent asymmetrical fetal growth retardation.
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PMID:Intrauterine growth retardation after long-term maternal salicylate administration in the rabbit. 379 57

The macromolecular structure of axonal membrane from dorsal funiculi of control and irradiated spinal cord of 45-day-old rats was examined with freeze-fracture electron microscopy. In control spinal cords, virtually all myelination is mediated by oligodendrocytes, and the internodal axonal membrane of these fibres displays highly asymmetrical partitioning of intramembranous particles (IMPs). The internodal P-face particle density is approximately 2350IMPs per micron 2, whereas the E-face IMP density is approximately 150 per micron 2. In control dorsal spinal roots, myelination is mediated by Schwann cells, and the ultrastructure of the internodal axolemma of the myelinated fibres is similar to that displayed by myelinated fibres of dorsal funiculi. On the internodal P-face of Schwann cell-myelinated fibres the IMP density is approximately 2350 per micron 2, whereas on the E-face the density is approximately 175 per micron 2. Irradiation of the lumbosacral spinal cord at 3 days of age results in a glial cell-deficient region within the spinal cord such that myelination in irradiated dorsal funiculi is delayed and subsequent myelination is mediated by both oligodendrocytes and Schwann cells. By 45 days of age, dorsal funiculi of irradiated spinal cords are well populated with fibres myelinated by oligodendrocytes and Schwann cells. However, fibres myelinated by oligodendrocytes display very thin myelin sheaths whereas Schwann cell-myelinated fibres exhibit myelin sheaths with normal thicknesses. Internodal membrane of fibres myelinated by Schwann cells and oligodendrocytes exhibit similar macromolecular structure, with approximately 2400 IMPs per micron 2 on P-faces and approximately 150 IMPs per micron 2 on E-faces. Occasional large (greater than 1.5 micron diameter) axons without glial-Schwann cell ensheathment are observed. These axons display a high density of P-face particles (approximately 2000 per micron 2) and a moderate density (approximately 350 per micron 2) of E-face IMPs on their fracture faces. These results demonstrate that CNS fibers exhibit similar axonal membrane ultrastructure irrespective of whether they are myelinated by Schwann cells or oligodendrocytes, or whether myelination is delayed. Moreover, when myelination does not occur, the axolemmal E-face IMP density, which may be related to the density of voltage-sensitive sodium channels, is not reduced.
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PMID:Effects of delayed myelination by oligodendrocytes and Schwann cells on the macromolecular structure of axonal membrane in rat spinal cord. 381 78

Guinea pig gastric mucous epithelial cells were isolated, enriched, cultured in collagen cups, and put into Ussing chambers for electrophysiological studies. The cultured mucous cell monolayers, which retain the morphology of surface cells found in the intact tissue, had a maximal resistance (R) of 272 +/- 12 omega X cm2 and a potential difference (PD) of -3.8 +/- 0.4 mV (apical negative) between 4 and 10 days later (n = 33). The current-voltage and conductance-concentration relationships of the cultures were both nonlinear (n = 12). In addition, NaCl concentration gradients across the monolayer also gave asymmetrical and nonlinear dilution potentials, with the side of lower chemical potential always becoming electrically negative (n = 10). Calculation of the average Cl(-)-to-Na+ permeability ratio at pH 7.4 was 1.35, indicating a slightly greater conductance of anions over cations. Amiloride (0.1-1.0 microM) had no effect on PD or R when given from the apical or basal side (n = 18), but at higher concentrations (0.1-1.0 mM) there was a decrease in the PD. 4,4'-Diisothiocyanostilbene-2,2'-disulfonic acid at 10(-4) M increased R from the apical side only (n = 14), and acetazolamide at 5 X 10(-4) M reduced the PD to -0.5 mV (n = 8). Only ouabain at 10(-4) M from the serosal side was effective in reducing the monolayer PD to zero. This culture preparation will prove useful for future studies in determining specific functions for this gastric cell type and how those functions relate to barrier function in the stomach.
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PMID:Transepithelial transport of guinea pig gastric mucous cell monolayers. 390 78


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