Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In a preparation of human leucocytes maintained in tissue culture fluid, increasing the extracellular zinc concentration leads to a significant increase in both ouabain-sensitive sodium efflux and in sodium influx. 2. Cell water and sodium content do not alter significantly with increasing extracellular zinc concentration. 3. A small increase in the ouabain-insensitive sodium efflux can be demonstrated when the external zinc concentration is raised from 0.75 mumol/l to 90 mumol/l.
Clin Sci Mol Med 1978 May
PMID:Effect of zinc on leucocyte sodium transport in vitro. 75 Jan 60

1. Plasma cadmium and zinc were determined by atomic absorption spectrophotometry in inferior venal caval or peripheral venous blood in thrity hypertensive patients and fifteen normal subjects. 2. The mean plasma cadium in hypertensive patients was significantly higher than in normal control subjects. 3. The plasma cadmium/zinc ratio was significantly greater in hypertensive patients. 4. There was a significant positive correlation between the plasma cadmium/zinc ratio and the mean arterial blood pressure.
Clin Sci Mol Med 1976 Nov
PMID:Plasma cadmium and zinc in human hypertension. 99 45

1. Distribution of zinc between the metalloprotein alpha 2-macroglobulin and albumin was determined in samples of serum obtained from twenty-three women in their third trimester of pregnancy and eighteen women who were not pregnant. 2. The decrease observed in total serum zinc in the group of pregnant women could be accounted for in large part by a decreased concentration of albumin-bound zinc. 3. The concentration of serum albumin was lower in the pregnant women, thus hypoalbuminaemia, which is often invoked to explain hypozincaemia in pathological situations, may in part account for hypozincaemia in pregnancy. 4. The affinity of albumin for zinc added to serum from pregnant women was less than that of albumin from non-pregnant women. This was determined by competition experiments between albumin and glycine for zinc. Decreased affinity of serum albumin for zinc may also contribute to the hypozincaemia associated with pregnancy.
Clin Sci Mol Med 1976 Dec
PMID:Diminished albumin binding of zinc in serum of pregnant women. 107 Apr 19

The ability of cations to modulate the binding of the sigma 1 receptor-selective ligand (+)-[3H]pentazocine to guinea pig cerebellum was investigated. Di- and trivalent cations biphasically inhibited (+)-[3H]pentazocine binding, revealing multiple affinity states. The rank order of potency of these cations (based on the high affinity component of inhibition) was Zn2+ > Co2+ >> La3+ = Ni2+ = Cd2+ = Mn2+ = Gd2+ > Ba2+ = Sr2+ >> Mg2+ > Ca2+. The inhibition of 1,3-[3H]di(2-tolyl)guanidine binding to the sigma 2 receptor by these cations differed qualitatively and quantitatively from their effects on (+)-[3H]pentazocine binding. Although monovalent cations decreased the Kd for (+)-[3H]pentazocine binding, divalent cations split (+)-[3H]pentazocine binding into low and high affinity components. The Bmax of the high affinity component decreased with increasing divalent cation concentrations. Both mono- and divalent cations significantly reduced the rate of association of (+)-[3H]pentazocine with the sigma 1 receptor without altering the dissociation rate. (+)-[3H]Pentazocine binding was not altered by guanine nucleotides or by treatment with cholera or pertussis toxins. However, nonselective cation channel blockers (cinnarizine, hydroxyzine, prenylamine, amiodarone, and proadifen) potently inhibited (+)-[3H]pentazocine binding. These results indicate that physiologically relevant concentrations of divalent cations allosterically modulate (+)-[3H]pentazocine binding to the sigma 1 receptor, to reveal multiple affinity states. These sites do not represent sigma 1 to sigma 2 subtype interconversion or ternary complex formation with guanine nucleotide-binding proteins. However, the rank order of cation potency and the inhibition of binding by cation channel blockers is consistent with a potential role for sigma receptors as constituents of cation channels.
Mol Pharmacol 1992 Nov
PMID:Modulation of (+)-[3H]pentazocine binding to guinea pig cerebellum by divalent cations. 127 78

A novel member of the zinc finger superfamily was cloned by virtue of its binding to cis-regulatory elements of a glia-specific gene, the myelin proteolipid protein (PLP) gene. Named MyTI (myelin transcription factor I), this gene is most highly transcribed in the developing nervous system, where expression precedes induction of its presumptive target, PLP. Low levels of MyTI transcripts can be detected in nonneural tissues only by polymerase chain reaction analysis. Zinc is a necessary cofactor for DNA binding of MyTI, as the zinc-chelating agent 1,10-orthophenanthroline eliminates binding activity. Zinc may stabilize the DNA-binding domain of MyTI by coordinating three cysteine and one histidine residue in a Cys-X5-Cys-X12-His-X4-Cys (C2-HC) arrangement. The MyTI protein has six fingers of the C2-HC class arranged in two widely separated clusters. These two domains of DNA binding can function independently and recognize the same DNA sequence, suggesting that MyTI may contribute to the higher-order structure of a target promoter by simultaneously binding both proximal and distal sites. The six fingers are highly conserved, suggesting that they arose from successive duplication events, while the linker regions diverge in size and sequence. Both amino acid sequence comparisons and secondary-structure predictions indicate that the C2-HC fingers of MyTI do not resemble the zinc-mediated loops of C2-H2 fingers, C2-C2 fingers, or Cx clusters. MyTI may therefore be the prototype of a new structural family of zinc-stabilized DNA binding proteins.
Mol Cell Biol 1992 Dec
PMID:Novel member of the zinc finger superfamily: A C2-HC finger that recognizes a glia-specific gene. 128 Mar 25

The long terminal repeat of Moloney murine leukemia virus (MuLV) contains the upstream conserved region (UCR). The UCR core sequence, CGCCATTTT, binds a ubiquitous nuclear factor and mediates negative regulation of MuLV promoter activity. We have isolated murine cDNA clones encoding a protein, referred to as UCRBP, that binds specifically to the UCR core sequence. Gel mobility shift assays demonstrate that the UCRBP fusion protein expressed in bacteria binds the UCR core with specificity identical to that of the UCR-binding factor in the nucleus of murine and human cells. Analysis of full-length UCRBP cDNA reveals that it has a putative zinc finger domain composed of four C2H2 zinc fingers of the GLI subgroup and an N-terminal region containing alternating charges, including a stretch of 12 histidine residues. The 2.4-kb UCRBP message is expressed in all cell lines examined (teratocarcinoma, B- and T-cell, macrophage, fibroblast, and myocyte), consistent with the ubiquitous expression of the UCR-binding factor. Transient transfection of an expressible UCRBP cDNA into fibroblasts results in down-regulation of MuLV promoter activity, in agreement with previous functional analysis of the UCR. Recently three groups have independently isolated human and mouse UCRBP. These studies show that UCRBP binds to various target motifs that are distinct from the UCR motif: the adeno-associated virus P5 promoter and elements in the immunoglobulin light- and heavy-chain genes, as well as elements in ribosomal protein genes. These results indicate that UCRBP has unusually diverse DNA-binding specificity and as such is likely to regulate expression of many different genes.
Mol Cell Biol 1992 Jan
PMID:Cloning of a negative transcription factor that binds to the upstream conserved region of Moloney murine leukemia virus. 130 93

In this study we addressed the question as to whether the mutagenesis by methylating agents is affected by the transcriptional activity of the damaged gene. An Epstein-Barr virus (EBV)-derived shuttle vector system was developed where the genetic target for mutation analysis, the bacterial gpt gene, is under the control of an eukaryotic inducible promoter in plasmid pF1-EBV and lacks the eukaryotic promoter in plasmid pF2-EBV. Two human cell lines that episomically maintain these shuttle vectors were established. In clone 6NT cells, which contain pF1-EBV plasmid, the gpt gene is actively transcribed and the transcription rate is regulated by zinc ions. In clone 3 cells, which harbor pF2-EBV plasmid, the gpt gene is not transcribed. Following treatment of both cell lines with the potent alkylating carcinogen N-methyl-N-nitrosourea (MNU), G.C to A.T transitions were the major mutagenic event, consistent with the miscoding potential of O6-methylguanine. The mutations were predominantly generated in the non-transcribed DNA strand of the active gpt gene. The same strand-bias was observed when the gpt gene was transcriptionally inactive, indicating that MNU-induced strand-specific formation of mutations is not due to transcription. Our data identify as major determinants of this phenomenon the sequence-specificity of MNU mutagenesis and the conformational properties of the target protein. Differences in mutation distribution were observed between the transcriptionally active and inactive gpt gene. This finding suggests that the organization of active genes in chromatin might modulate DNA alkylation and/or DNA repair.
J Mol Biol 1992 Feb 05
PMID:N-methyl-N-nitrosourea-induced mutations in human cells. Effects of the transcriptional activity of the target gene. 150 35

The initial water proteolysis step in the proton transfer "half-reaction" of human carbonic anhydrase I is simulated using the empirical valence bond method in combination with free energy perturbation molecular dynamics calculations. A free energy profile for the enzyme catalysed reaction and the corresponding pKa associated with ionization of the zinc-bound water is calculated. The obtained pKa value of 7 to 8 appears to be in good agreement with experimental observations and the calculated rate constant for this step is also compatible with kinetic data. The simulations clearly emphasize the important electrostatic effect associated with the catalytic zinc ion.
J Mol Biol 1992 Mar 05
PMID:Computer simulation of the initial proton transfer step in human carbonic anhydrase I. 131 6

The effect of regucalcin, a calcium-binding protein isolated from rat liver cytosol, on deoxyuridine 5'-triphosphatase (dUTPase) in the cytosol of rat liver was investigated. Addition of Ca2+ up to 5.0 microM to the enzyme reaction mixture caused a significant decrease of dUTPase activity, while Zn2+, Cd2+, Co2+, Al3+, Mn2+ and Ni2+ (10 microM) did not have an appreciable effect. The Ca(2+)-induced decrease of dUTPase activity was reversed by the presence of regucalcin; the effect was complete at 1.0 microM of the protein. Regucalcin had no effect on the basal activity of the enzyme. Meanwhile, the reversible effect of regucalcin on the Ca2+ (10 microM)-induced decrease of dUTPase activity was not altered by the coexistence of Cd2+ or Zn2+ (10 microM). The present data suggest that liver cytosolic dUTPase is uniquely regulated by Ca2+ of various metals, and that the Ca2+ effect is reversed by regucalcin.
Mol Cell Biochem 1992 Mar 04
PMID:Reversible effect of calcium-binding protein regucalcin on the Ca(2+)-induced inhibition of deoxyuridine 5'-triphosphatase activity in rat liver cytosol. 131 24

Two radical adduct species have been detected in the bile of living rats treated with halothane and phenyl-N-t-butylnitrone (PBN). The treatment of rats with 12% oxygen was required for radical adduct detection. Analysis of the corresponding EPR spectra obtained when deuterated PBN and deuterated halothane or [2-13C]halothane was used shows that these two species result from the spin trapping of two halothane-derived free radicals. Coupling constants were aN = 15.72 G, a beta H = 2.09 G, a gamma H = 0.79 G, and aF = 0.63 G(3F) and aN = 15.16 G, a beta H = 4.14 G, a gamma H = 0.48 G, and aF = 0.3 G(3F) for the two species. Two radical adducts with similar coupling constants were detected when halothane was reduced by zinc dust in the presence of PBN, suggesting that the formation of these two distinct species from halothane can be attributed to the one-electron reduction of halothane and the formation of diastereomeric radical adducts. The identification of both radical adducts as halothane-derived species indicates that there is no in vivo EPR evidence for lipid radical formation during halothane intoxication, as had previously been reported.
Mol Pharmacol 1992 May
PMID:Free radical metabolism of halothane in vivo: radical adducts detected in bile. 131 2


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