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)

We used the whole-cell configuration of the patch-clamp technique and cultured ventricular myocytes from 7-day embryonic chicks to test the hypothesis that sialic acid residues (NANA) constitute the negative surface charge associated with delayed rectifier potassium channels. Delayed rectifier current (iK) was elicited at potentials between -40 and +60 mV. The existence of negative fixed charges close to the "gating sensor" was confirmed by a 6.8-mV negative shift of the half-activation potential (V1/2) following a 10-fold reduction of divalent cations and a 22.6-mV position shift following the addition of 10 mM NiCl2. An 8.4-mV increase in the Boltzmann equation slope factor (k) in the former experiment and a 5.5-mV decline in the latter suggested that the surface charge is not uniformly distributed. We used a high performance liquid chromatography procedure to detect freed sarcolemmal NANA and found that 71-88% was released by neuraminidase (0.2-2.0 U/ml) during 1-h treatments. Such treatments had no significant effect upon the amplitudes of iK or V1/2. On the other hand, k was increased significantly by the enzyme (2.0 U/ml), but only when Ca2+ was present. Finally, 1-h pre-treatments with neuraminidase (2.0 U/ml) had no effect on the positive shift of V1/2 induced by Ni2+. We conclude that although sarcolemmal NANA may bind Ca2+, it does not constitute the surface charge of delayed rectifier potassium channels.
J Mol Cell Cardiol 1990 Nov
PMID:Sialic acid and the surface charge of delayed rectifier potassium channels. 228 87

We have determined the structure of a T-state haemoglobin in which the haem groups of the beta subunits have carbon monoxide bound, and the alpha subunits have nickel replacing the haem iron and are ligand-free. The structural adjustments on binding ligand in the T state are in the same direction as those associated with the quaternary transition, and a translational shift of the haem is severely restricted. We explain how these observations may account for the low ligand affinity of the beta haem of T-state haemoglobin.
J Mol Biol 1990 Jul 05
PMID:Structure of deoxy-quaternary haemoglobin with liganded beta subunits. 237 Jun 69

The depolarization of frog sciatic nerves by the Na channel-activating toxins, batrachotoxin and veratridine, was studied using the sucrose-gap technique. To study the interaction between the activators and the gating processes of Na channels, we measured the depolarizations of unstimulated nerves, of nerves during repetitive stimulation, and of nerves whose Na channel inactivation process had been pharmacologically modified. Stimulation enhanced the rates of depolarization by the activators but did not effect the steady state depolarization values. Of the three inhibitors of Na channel inactivation that were tested (Leiurus alpha-scorpion toxin, chloramine T, and Ni2+), only Leiurus toxin enhanced the potencies of the activators. Neither chloramine T nor Ni2+ had any effect on the steady state level of depolarization produced by either activator. Both chloramine T and Ni2+, however, enhanced the rate of batrachotoxin action, although neither affected the rate of veratridine action. Leiurus toxin also potentiated the effects of the activators in chloramine T-treated nerves. We tested the interaction between the Na channel activators and a class of agents, local anesthetics, that stabilize a non-conducting state of the Na channel. The presence of lidocaine inhibited the depolarization produced by addition of either activator, although the addition of lidocaine subsequent to the development of batrachotoxin-induced depolarization produced repolarization very weakly and slowly. We also found that the lidocaine homologue, RAC 109I, was about 3 times as potent as its stereoisomer, RAC 109II, in its ability both to reduce the compound action potential amplitude and to inhibit the veratridine-induced depolarization.
Mol Pharmacol 1986 May
PMID:The interaction between the activator agents batrachotoxin and veratridine and the gating processes of neuronal sodium channels. 242 36

To determine whether P0 myelin glycoprotein mRNA is expressed in Schwann cells that ensheath neurons and do not form myelin, we probed aldehyde-fixed vibratome sections of developing and adult trigeminal ganglia with a biotinylated P0 cDNA. For probe detection, vibratome sections were treated with nickel-enhanced horseradish peroxidase (HRP). At each age, some vibratome sections were used to count numbers of HRP-positive and -negative satellite cells. The percentages of HRP-positive satellite cells at 2, 7, and 15 days were 22%, 30% and 14%. None was positive at 30 days or in the adult. Other vibratome sections were embedded for light and electron microscopic study. In semithin sections from ganglia removed from 2-day-old rats, small dot-like densities of HRP were located in perinuclear regions of a few perineuronal Schwann cells. In 7-day-old ganglia, more of these Schwann cells contained HRP. In thin sections studied with the electron microscope, peroxidase was found in cytoplasmic regions enriched in granular endoplasmic reticulum and ribosomes. At 2 and 7 days, HRP densities in perinuclear regions were larger and more numerous than at 15 days. No signal was detected in 30 day or adult perineuronal Schwann cells. The results show that early in postnatal development, P0 mRNA is expressed in some Schwann cells that ensheath neurons, that do not contain immunocytochemically detectable levels of P0 and that do not ever form myelin.
Brain Res Mol Brain Res 1989 Mar
PMID:Non myelin-forming perineuronal Schwann cells in rat trigeminal ganglia express P0 myelin glycoprotein mRNA during postnatal development. 246 27

Evidence is presented to support our hypothesis that an alpha-macroglobulin (alpha M) produced by lung macrophages serves as a specific binding protein for platelet-derived growth factor (PDGF) from these same macrophages. Culture medium "conditioned" by alveolar macrophages was fractionated by gel filtration according to molecular weight. Proteins larger than 200 kD were bound to greater than 50% of the macrophage-derived PDGF (MD-PDGF) that was extractable by 1 M acetic acid. Another approximately 25% was bound to fractions at approximately 150 kD, and approximately 20% remained unbound. The two high molecular weight fractions inhibited approximately 40% of specific [125I]PDGF binding to rat lung fibroblasts, whereas other fractions did not block PDGF binding to its receptor. Only the greater than 200 kD fractions inhibited the binding of PDGF antisera to purified human PDGF by 20% of control and exhibited specific complex formation and coelution on a gel filtration column with [125I]PDGF. The macrophage-derived alpha M (MD-alpha M) was separated from other macrophage-derived proteins by nickel-affinity chromatography and exhibited clear characteristics of alpha Ms, i.e., cross-reactivity with antibodies to human alpha 2-macroglobulin (alpha 2M) on immunoblots as well as gel migration corresponding to the electrophoretic mobility of the protease-bound "fast" and protease-unbound "slow" forms of human alpha 2M. Nickel-bound protein identified as an alpha M was bound to greater than 50% of the acid-extractable MD-PDGF in macrophage-conditioned medium, supporting the view that the greater than 200 kD protein separated by gel filtration is an alpha M.(ABSTRACT TRUNCATED AT 250 WORDS)
Am J Respir Cell Mol Biol 1989 Sep
PMID:Alpha-macroglobulin secreted by alveolar macrophages serves as a binding protein for a macrophage-derived homologue of platelet-derived growth factor. 248 18

(trans)-2-(3-Methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5- trimethoxyphenyl)tetrahydrofuran (L-659,989) is a potent and orally active platelet-activating factor (PAF)-specific and competitive receptor antagonist. The 2,5-tritium-labeled L-659,989 ([3H]L-659,989) specifically binds to rabbit platelet membranes with an equilibrium dissociation constant (KD) of 1.60 +/- 0.20 nM in 10 mM MgCl2. Several selected PAF analogs and PAF receptor antagonists show equilibrium inhibition constants roughly similar to those found in the specific [3H]PAF binding assay. Other pharmacological agents with no PAF antagonistic activities do not inhibit the specific binding of [3H]L-659,989. K+ and divalent cations such as Mg2+, Ca2+, and Mn2+ potentiate the specific [3H]L-659,989 binding. Na+ and Li+ also enhance but GTP shows no effect on the specific binding of [3H]L-659,989. However, Ni2+ inhibits the specific binding. Scatchard analysis demonstrates that the potentiating effect of these cations is due to an increase in the detectable receptor number for L-659,989. In 10 mM MgCl2 [3H]L-659,989 shows higher receptor number than [3H]PAF. Under various ionic conditions with or without GTP, in which [3H] L-659,989 binding remains approximately the same, C16-PAF shows different potencies in competing against the specific [3H] L-659,989 binding. These results demonstrate the existence of multiple conformational states of the PAF-specific receptor. The variation in the detectable receptor number under different conditions is due to the coexistence of the high and low affinity states and the fact that the low affinity state(s) of the receptor with KD value(s) possibly in the micromolar range cannot be detected in the Scatchard analysis with the radioligand at nanomolar concentrations. In the presence of 150 mM NaCl and 1 mM GTP, receptors exist in a single conformational state with an equilibrium dissociation constant (KB) of 0.931 microM for PAF.
Mol Pharmacol 1989 Jan
PMID:Characterization of platelet-activating factor (PAF) receptor by specific binding of [3H]L-659,989, a PAF receptor antagonist, to rabbit platelet membranes: possible multiple conformational states of a single type of PAF receptors. 253 68

We studied induction of cytotoxicity and morphological transformation in C3H/10T1/2 Cl 8 (10T1/2) mouse embryo fibroblasts by soluble and insoluble carcinogenic nickel compounds. Soluble nickel sulfate and nickel chloride caused dose-dependent cytotoxicity in the concentration range from 0.5 microM to 100 microM after 48 hr treatments, but neither compound induced morphological transformation even at concentrations causing up to 94% cytotoxicity. Insoluble nickel subsulfide, nickel monosulfide, and nickel oxide caused dose-dependent cytotoxicity and a low, dose-dependent frequency of morphological transformation in the concentration ranges from 0.5 to 40 microM, 5 to 50 microM, and 50 to 400 microM, respectively, after 48 hr exposure of cells to these compounds. Foci were predominantly of type II morphology; type III foci were rare. The insoluble nickel compounds studied caused no induction of base substitution mutations to ouabain resistance in 10T1/2 cells over concentration ranges that induced morphological transformation. Nickel subsulfide and nickel monosulfide were taken into cells by phagocytosis, since particles were visible in intracytoplasmic vacuoles. Numerous nickel oxide particles were found associated with cells, but true phagocytic uptake was difficult to detect since no vacuoles were observed. We twice cloned type II and type III foci induced by insoluble nickel compounds, established independent cell lines, and characterized their phenotypes. Four of seven of these cell lines had three- to fourfold increased saturation densities compared to 10T1/2 cells, formed type II and type III foci in reconstruction assays, and grew in soft agarose. One cell line induced by nickel oxide formed tumors in nude mice. These data indicate that insoluble carcinogenic nickel compounds induced type II foci in 10T1/2 cells, some of which were tumorigenic, and that the 10T1/2 cell system is suitable for studying mechanisms of nickel compound-induced morphological transformation in mammalian cells.
Environ Mol Mutagen 1989
PMID:Morphological and neoplastic transformation of C3H/10T1/2 Cl 8 mouse embryo cells by insoluble carcinogenic nickel compounds. 254 61

Membrane currents and changes in intracellular calcium ion concentration ([Ca2+]i) have been recorded that can be attributed to the operation of an electrogenic, voltage-dependent sodium-calcium (Na-Ca) exchanger in mammalian heart cells. Single guinea-pig ventricular myocytes under voltage clamp were perfused internally with the fluorescent Ca2+-indicator, fura-2, and changes in [Ca2+]i and membrane current that resulted from Na-Ca exchange were isolated through the use of various organic channel blockers (verapamil, TTX), impermeant ions (Cs+, Ni2+), and inhibitors of sarcoplasmic reticulum (ryanodine). The I-V relation of Na-Ca exchange was obtained from the Ni2+-sensitive current elicited by ramp repolarization from +90 mV to -80 mV. Ramps were sufficiently rapid that little change in [Ca2+]i occurred during the ramp. The (constant) [Ca2+]i during the ramp was varied over the range 100 nM to 1000 nM by varying the amplitude and duration of a pre-pulse to the ramp. The reversal potential of the Ni2+-sensitive ramp current varied linearly with 1n[( Ca2+])i. The I-V relations at different [Ca2+]i over the range -60 mV to +140 mV were in reasonable accord with the predictions of a simple, simultaneous scheme of Na-Ca exchange, on the basis that only [Ca2+]i had changed. The relationship between [Ca2+]i and current at a constant membrane voltage was also in accord with this scheme. We suggest that Ca2+-fluxes through the exchanger during the cardiac action potential can be understood quantitatively by considering the binding of Ca2+ to the exchanger during the [Ca2+]i-transient and the effects of membrane voltage on the exchanger.
Mol Cell Biochem 1989 Sep 07
PMID:Sodium-calcium exchange in mammalian heart: current-voltage relation and intracellular calcium concentration. 255 26

The interaction of DNA with divalent metal ions: Ba2+, Mg2+, Mn2+, Ni2+, Cu2+ in solutions at different ionic strengths mu was investigated. The combination of following methods: flow birefringence, viscometry, UV-spectroscopy and circular dichroism made possible to follow the state of the secondary and tertiary structure of the DNA molecule during its interaction with ions. The presence of divalent ions in solution affects the hydrodynamic properties of DNA only at low mu. At high mu the difference in the action of mono- and divalent ions disappears. The persistence length of DNA does not change during the experiment. It is shown that the Mg2+ and Ba2+ ions interact only with phosphate groups of DNA but Mn2+, Ni2+, Cu2+ ions interact also with the nitrogen bases of the macromolecule.
Mol Biol (Mosk)
PMID:[A study of the molecular mechanism of DNA interaction with divalent metal ions]. 258 10

Rabbit histidine-rich glycoprotein (HRG) binds low-spin heme and metals tightly at several sites that contain histidine. As part of an on-going effort to define and locate the binding sites for these and the other ligands of HRG, the sequence: NH2-Gly-His-Phe-Pro-Phe-His-Trp-... was found in a 16 kDa heme-binding peptide isolated from HRG. The spacing of the histidyl residues in this peptide, which contains the C-terminal 79 residues of HRG, together with molecular modeling suggested that this sequence might constitute one heme binding site of HRG by accommodating heme in a bis-histidyl linkage. Three peptides based on this sequence (I, HFPFHW; II, WHFPFH; and III, HFGFHW) were synthesized, and their ability to bind heme and metals examined. All three peptides bind heme as demonstrated by the changes produced in the absorbance of heme when mixed with the peptides. Substituting glycine for proline in the central position or moving the location of the tryptophan did not affect heme binding. The apparent Kd's of the mesoheme/peptide I, II and III complexes are 75 +/- 25 microM, indicative of heme binding approximately 100 times less avid than the mesoheme/HRG complex (Kd ca. 1 microM), but nearly 1000 times tighter than that of the mesoheme/histidine complex (Kd ca. 60 mM). The absorbance spectra of the mesoheme/peptide complexes, the loss of binding caused by modification of histidine residues, and the pH dependence of heme binding, all indicate that heme forms a low spin, bis-histidyl type of complex with these peptides, like that formed with HRG itself. Copper, but not cadmium or nickel, was an effective inhibitor of heme binding by the peptides. The sequence of HRG congruent with the sequence of peptide I is proposed to be one heme- and metal-binding site of rabbit HRG.
J Mol Recognit 1989 Nov
PMID:A heme- and metal-binding hexapeptide from the sequence of rabbit plasma histidine-rich glycoprotein. 263 1


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