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Query: UNIPROT:P06889 (Mol)
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(i) Trace element concentrations in soft tissue of the benthic bivalve, Corbicula fluminea, from the San Joaquin River and its major tributaries were examined during the primary irrigation season in relation to the spatial variation in concentrations of major, minor and trace constituents in riverwater and sediments. (ii) Selenium concentrations in Corbicula from perennial flow reaches of the San Joaquin River and its major tributaries varied directly with the solute (less than or equal to 0.45 microns) Se concentrations of riverwater. Elevated concentrations occurred in clams from sites with substantial discharge originating as subsurface drainage and irrigation return flows. Both tissue and solute Se concentrations declined from June through the end of the primary irrigation season. (iii) Arsenic concentrations in Corbicula from perennial flow reaches of the San Joaquin River varied directly with the HNO3-extractable (pH 2) As:Fe ratio of suspended matter, providing evidence that sorption to oxyhydroxide surfaces is an important control on the biological availability of As. However, Corbicula from several tributaries draining alluvium derived from the Sierra Nevada had lower As concentrations than would be predicted by the relation developed for perennial flow sites of the San Joaquin River. Arsenic concentrations in Corbicula from the Tuolumne and Merced Rivers and upstream reaches of the San Joaquin River were higher than in clams from the downstream perennial flow reaches of the San Joaquin River. Concentrations of As in clams from downstream perennial flow reaches of the San Joaquin River increased from June through the end of the primary irrigation season. (iv) Mercury concentrations in Corbicula were elevated in upstream reaches of the San Joaquin River, in the Merced and Tuolumne Rivers, and in tributaries draining the Coast Ranges. Mean Cd and Cu concentrations in Corbicula were elevated in the Merced and Tuolumne Rivers, Orestimba Creek and a perennial flow reach of the San Joaquin River which receives water directly from the Delta Mendota Canal. Concentrations of Ni in clams from the San Joaquin River decreased downstream of the Delta Mendota Pool. (v) Boron and Mo were not accumulated by Corbicula despite high solute concentrations (means as high as 2960 micrograms Bl-1 and 9 micrograms Mol-1) in riverwater during the primary irrigation season. This bivalve may not be an appropriate bioindicator of B and Mo enrichment. Concentrations of Cr, Pb, Ag, V and Zn in Corbicula exhibited little geographic variability in the drainage. (vi) Regression analysis revealed no clear evidence of synergistic or antagonistic interactions among As, Cd, Cu, Hg, Ni and Se in their uptake by Corbicula.
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PMID:Trace elements in Corbicula fluminea from the San Joaquin River, California. 208 41

In order to trace possible accumulations of mercury, three vervet monkeys received occlusal amalgam fillings, three others maxillary bone implants of amalgam, and three untreated monkeys served as controls. One year later all animals were sacrificed by transcardial perfusion with glutaraldehyde. Tissue sections from different organs were subjected to silver amplification by autometallography and analyzed at light and electron microscopical levels. It was found that amalgam fillings (total, 0.7-1.2 g) caused deposition of mercury in the following tissues: spinal ganglia, anterior pituitary, adrenal, medulla, liver, kidneys, lungs, and intestinal lymph glands. In monkeys with maxillary silver amalgam implants (total, 0.1-0.3 g), mercury was found in the same organs except for liver, lungs, and intestinal lymph glands. Organs from the three control animals were devoid of precipitate. To evaluate whether silver released from the corroding amalgam fillings added to the staining pattern, tissue sections were exposed to potassium cyanide prior to being autometallographically developed. This treatment removes all traces of silver, leaving mercury sulfide accumulation untouched. By comparing sections that had been exposed to cyanide with untreated parallels no difference was seen in the pattern confirming that mercury was the only catalyst present in the tissue. These results strongly support what has been suggested previously that dental fillings in primates cause absorption of mercury released from amalgam fillings through lungs and intestinal tract, and that depending on exposure mercury is distributed to most organs and will eventually be found in the central nervous system. The present data also show that silver released from the corroding filling is not absorbed.
Exp Mol Pathol 1990 Jun
PMID:Traces of mercury in organs from primates with amalgam fillings. 211 6

The etiology of mercury-induced porphyrinuria was investigated by testing the hypothesis that mercuric ions (Hg2+) promote free radical-mediated oxidation of reduced porphyrins (porphyrinogens) by compromising the antioxidant potential of endogenous thiols, particularly GSH. Studies in vitro demonstrated that porphyrinogens (uroporphyrinogen and coproporphyrinogen) readily undergo H2O2-dependent oxidization in the presence of Fe3(+)-EDTA and that this action is attenuated by GSH at biologically relevant concentrations (0.5-10 mM). At low concentrations, Hg2+ complexes with GSH in a 1:2 molar ratio to decrease the antioxidant effect of GSH. However, at Hg2+ concentrations approaching saturation-complexation with available GSH, stimulation of porphyrinogen oxidation to 2 to 3 times that mediated by the H2O2/Fe3(+)-dependent system alone is observed. Stimulation of porphyrinogen oxidation by Hg2+ plus GSH increases in a dose-related manner with the concentration of H2O2 in the reaction mixture but is independent of the presence of iron. No porphyrinogen oxidation is observed in reaction mixtures containing H2O2 and either Hg2+ or GSH alone or when Hg+ is substituted for Hg2+. Studies with reactive oxidant scavengers and ESR spectroscopy suggest the participation of free radical species in Hg:GSH-mediated porphyrinogen oxidation. A mechanism involving ligand exchange between Hg2+ and GSH, which leads to formation of GS radicals and subsequent propagation of reactive oxygen-based radical species, is proposed. These studies support the view that Hg2+ both compromises the antioxidant potential of GSH and promotes formation of reactive species via thiol complexation. These findings suggest a mechanistic basis underlying the porphyrinogenic as well as tissue-damaging properties of mercuric ions.
Mol Pharmacol 1990 Aug
PMID:Stimulation of porphyrinogen oxidation by mercuric ion. I. Evidence of free radical formation in the presence of thiols and hydrogen peroxide. 216 5

A new affinity chromatographic procedure for the separation of transcriptionally active nucleosomes has been used to study the changes that take place in chromatin structure along the c-fos and c-myc genes when RNA synthesis is inhibited. Mercury-affinity chromatography separates the sulfhydryl-reactive nucleosomes of transcriptionally active genes from the compactly beaded, non-reactive nucleosomes of transcriptionally inert DNA sequences. The new procedure also discriminates between nucleosomes that have "unfolded" to reveal the previously shielded SH groups of histone H3 and nucleosomes that bind to the mercury column because of their association with thiol-containing non-histone proteins located in the transcription unit. Both classes of Hg-bound nucleosomes contain the c-fos and c-myc sequences, but only when they are being transcribed. We compared the effects of alpha-amanitin and actinomycin D on the transcription of c-fos and c-myc with the effects of each inhibitor on the distribution of the corresponding oncogenic DNA sequences in the chromatographically separated nucleosome fractions. It was found that the inhibition of RNA polymerase II by alpha-amanitin (added at the peaks of c-fos or c-myc expression in serum-stimulated BALB/c 3T3 cells) resulted in a rapid loss of affinity of the oncogene-containing nucleosomes for the mercury column. There was no corresponding effect on the mercury-binding properties of nucleosomes containing 28 S ribosomal gene sequences, which continue to be transcribed by amanitin-resistant RNA polymerase I. Therefore, the binding of the c-fos and c-myc nucleosomes to the mercury column seems to depend upon reversible structural changes associated with their transcription. Surprisingly, there was no corresponding loss of affinity of the c-fos and c-myc nucleosomes for the mercury column when actinomycin D was employed to inhibit RNA synthesis, despite the fact that transcription of both genes had been arrested abruptly. Measurements of [3H]actinomycin D binding show its preferential intercalation into the transcriptionally active nucleosomes. We suggest that the intercalation of actinomycin D into the DNA of active nucleosomes can lock the transcription complex into an "unfolded" but potentially active configuration. This was confirmed by run-off transcription assays showing a restoration of c-fos and c-myc RNA synthesis when actinomycin D was displaced by proflavine.
J Mol Biol 1990 Apr 05
PMID:Reversible and irreversible changes in nucleosome structure along the c-fos and c-myc oncogenes following inhibition of transcription. 232 30

The interleukin 1 (IL-1) family of proteins has a central role in modulating immune and inflammatory responses. Two major IL-1 proteins, designated alpha (IL-1 alpha) and beta (IL-1 beta), are produced by activated macrophages and other cell types. In an effort to understand the similarities and differences in the physicochemical and functional properties of these two proteins, a program was initiated to determine their structures. Crystals of IL-1 alpha were grown, and the three-dimensional structure at 2.7-A resolution was solved. The technique of multiple-wavelength anomalous dispersion (MAD) with the selenomethionine form of IL-1 alpha was utilized in combination with a single mercury derivative to provide the starting phases. Partial refinement of the IL-1 alpha model has been performed as well. The overall structure is composed of 14 beta-strands and a 3(10) helix. The core of this structure is a capped beta-barrell that possesses 3-fold symmetry and displays a topology similar to that observed for IL-1 beta [Priestle, J. P., et al. (1988) EMBO J. 7, 339-343] and soybean trypsin inhibitor (STI) [McLachlan, A. D. (1979) J. Mol. Biol. 133, 557-563]. In this paper, the overall structure of IL-1 alpha and the nature and fidelity of the internal 3-fold symmetry are discussed. Comparisons with IL-1 beta and STI are made within these contexts.
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PMID:Structure of interleukin 1 alpha at 2.7-A resolution. 234 41

Previous studies have shown that mercuric ion (Hg2+) reacts with GSH and H2O2 in vitro to form reactive species capable of oxidizing reduced porphyrins (porphyrinogens). This effect is independent of the presence of iron in the reaction mixture. The present studies demonstrate that Hg2+ and GSH can interact in biologically relevant concentrations with H2O2 generated by the mitochondrial electron transport chain to promote oxidation of porphyrinogens via comparable mechanisms. Mitochondria from rat liver or kidney readily oxidize uroporphyrinogen when H2O2 production is stimulated by the presence of a respiratory chain substrate (NADH, succinate) and an electron transport inhibitor (e.g., NaN3). Porphyrinogen oxidation by mitochondria is significantly increased by the addition of Hg2+ and GSH, in a molar ratio of approximately 3:5, to the reaction mixture. Stimulation of porphyrinogen oxidation in the presence of Hg2+ plus GSH increases proportionately with the concentration of mitochondrial protein in the reaction cuvettes but decreases with diminished H2O2 production by the electron transport chain. Studies with reactive oxidant scavengers suggest the participation of reactive oxygen species in Hg plus GSH stimulation of mitochondrial porphyrinogen oxidation. These findings support the hypothesis that Hg2+ and GSH interact with mitochondria-generated H2O2 to promote propagation of reactive oxidants or other free radical species, which, in turn, oxidize reduced porphyrins proximal to mitochondrial membranes. These results suggest a mechanistic explanation for the porphyrinogenic action of mercury compounds, as well as for the oxidative damage to target cell constituents associated with mercury exposure.
Mol Pharmacol 1990 Aug
PMID:Stimulation of porphyrinogen oxidation by mercuric ion. II. Promotion of oxidation from the interaction of mercuric ion, glutathione, and mitochondria-generated hydrogen peroxide. 238 33

Methyl mercury (MeHg) inhibited the overall RNA synthetic reaction of HeLa RNA polymerase II. However, when RNA chain initiation was allowed to occur in its absence, MeHg stimulated the rate of the subsequent elongation stage of the reaction. Chain elongation with both double-stranded and single-stranded DNA templates was stimulated. This stimulatory effect was specific for MeHg; both p-hydroxymercuribenzoate and HgCl2 inhibited chain elongation (to about the same degree as they inhibited the overall reaction). The stimulatory effect was also specific for the HeLa polymerase; with Escherichia coli RNA polymerase, MeHg inhibited elongation (to the same degree as it inhibited the overall reaction).
Mol Pharmacol 1988 Nov
PMID:Methyl mercury stimulates chain elongation by purified HeLa RNA polymerase II. 246 8

We report studies on deletion mutants of the regulatory region of the mercuric ion resistance (mer) genes of transposon Tn501, isolated from Pseudomonas aeruginosa. Transcription of the mer genes in Escherichia coli from the promoter Pmer is regulated both positively (in the presence of mercuric salts) and negatively (in their absence) by the product of the merR gene. The merR gene is transcribed divergently with respect to the other mer genes, and negatively regulates its own synthesis. The experiments described here suggest that both positive and negative regulation by MerR, as well as its autoregulation, are largely mediated by MerR binding to a single site on DNA. This site contains a hyphenated dyad symmetrical sequence centred 24 base-pairs before the start of the mer transcript. Additional sites may be involved in full repression of the mer and merR promoters. Studies on deletions of the Pmer promoter show that the -35 sequence is not required for constitutive activity. An alternative -10 sequence may be used in the absence of the -35 and normal -10 sequences, but the properties of a point mutation indicate that, in the presence of the -35 sequence, the normal -10 sequence is required for promoter activity. A model for the regulation of expression of the mercury resistance genes by mercuric ions and the MerR protein is discussed.
J Mol Biol 1989 Jan 20
PMID:Regulation of transcription in Escherichia coli from the mer and merR promoters in the transposon Tn501. 253 25

The ability to determine protein structures by X-ray crystallography is often thwarted by the difficulty of finding isomorphous heavy-atom derivatives. The crystal structure of the site-specific recombinase, resolvase, has been difficult to determine for this reason. We have overcome this problem by introducing 13 single cysteine substitutions into the resolvase catalytic domain using oligonucleotide mutagenesis. The mutant proteins were screened for their ability to crystallize into the orthorhombic form and bind mercury ions isomorphously. Two mutant proteins provided excellent heavy-atom derivatives. This approach should be of general use and particularly helpful in cases where traditional methods have failed to produce a derivative.
J Mol Biol 1989 Aug 20
PMID:Preparation of heavy-atom derivatives using site-directed mutagenesis. Introduction of cysteine residues into gamma delta resolvase. 255 82

Kainate receptors are one of the major subtypes of excitatory amino acid receptors in the vertebrate central nervous system. Using Xenopus oocytes injected with RNA from human temporal cortex, it is possible to detect electrophysiologically the expression of this receptor subtype in these cells. Ions of the group IIb elements, particularly mercuric ions, are highly potent, noncompetitive inhibitors of these human brain kainate receptors. Mercury-containing sulfhydryl reagents are also very effective, irreversible blockers of the kainate-gated currents of these oocytes. The recovery of kainate-activated currents after washout of Hg2+ is slow and incomplete relative to that seen after treatment either with Cd2+ or Zn2+. Cysteine or dithiothreitol can accelerate this recovery of kainate-inducible currents after Hg2+ inhibition. Besides the toxicological implications of these results, mercury compounds may be useful for future studies of the structure and physiology of the kainate receptor-channel complex.
Mol Pharmacol 1989 Oct
PMID:Mercuric ions are potent noncompetitive antagonists of human brain kainate receptors expressed in Xenopus oocytes. 257 61


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