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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The extent of mercury mobilisation was recorded from various tissues (brain, spinal cord, liver and kidney) of male mice administered with a daily dose of methylmercury chloride (1 mg/kg) for seven days. For this purpose 10 groups of animals were intoxicated. Out of these, one group was sacrificed on 8th day and one group was kept without toxicant for another seven days before sacrificing on 15th day. To the rest of the groups were given a daily dose of N-acetyl-DL-homocysteine thiolactone (NAHT), glutathione (GSH), vitamin B Complex and E, applied either alone or in combinations. All these animals were sacrificed on the 15th day. The mercury clearance rate during thiols, vitamins and their co-administration was examined. Study shows that both the vitamins were able to increase mercury elimination from the nervous and non-nervous tissues. Their combination with NAHT was not suitable as mercury level was increased in all the tissues except kidney as compared to NAHT alone treated group. However, vitamin B Complex combination with glutathione was much advantageous. It is concluded from the overall study that application of vitamin B Complex and E either alone or in combination with GSH is quite suitable for methylmercury post-therapy.
Cell Mol Biol (Noisy-le-grand) 1993 Mar
PMID:Ameliorative capacities of vitamins and monothiols administered alone or in combinations in methylmercury mobilisation in nervous and non-nervous tissues of mice. 851 76

A histochemical technique has been used to reveal mercury deposits in the hypothalamic arcuate nucleus and median eminence of adult male rats. After exposure to long-term, low-level or short-term, high-level mercury vapor, silver-enhanced mercury grains were found in neurons of the arcuate nucleus. In addition mercury deposits were found in tanycytes, ciliated ependymal cells, and in the walls of capillaries. The mechanisms underlying uptake and possible induction of toxic effects are discussed.
Exp Mol Pathol 1993 Jun
PMID:Mercury in the rat hypothalamic arcuate nucleus and median eminence after mercury vapor exposure. 851 47

Adult male Wistar rats were exposed to mercury vapor, 50 micrograms Hg/m3, 6 hr/day, 5 days/week, over 1-, 2-, 3-, 4-, 6-, and 8-week periods. Sections from the spinal cord and dorsal root ganglia from spinal levels C1, C5, T6, and L1 were stained with the autometallographical technique and the distribution of mercury deposits described at light and electron microscopical levels. A quantitative analysis of the amount of mercury in blocks of the spinal cord was performed using cold vapor atomic absorption spectrophotometry. After an exposure period of 2 weeks, silver-enhanced mercury grains could be observed in spinal cord neurons located in Rexed laminae IV-X. Ventral horn motoneurons were heavily stained in all of the spinal cord segments. Ependymal cells and glial cells of both the spinal gray and white matter contained cytoplasmatic mercury accumulations in rats exposed to mercury vapor for 4 weeks. In the dorsal root ganglia, only ganglion cells showed a faint mercury staining and the amount of staining was notably less than that seen in the ventral horn motoneurons. At the ultrastructural level, mercury was seen primarily within lysosomes of target cells. The quantitative mercury measurements demonstrated that spinal cords from rats exposed to mercury vapor for 6 or 8 weeks contained a significantly higher concentration of mercury than those from control animals.
Exp Mol Pathol 1993 Jun
PMID:Detection of mercury in rat spinal cord and dorsal root ganglia after exposure to mercury vapor. 851 48

The small (116 amino acids) inner membrane protein MerT encoded by the transposon Tn501 has been overexpressed under the control of the bacteriophage T7 expression system. Random mutants of MerT were made and screened for loss of mercuric ion hypersensitivity. Several mutant merT genes were selected and sequenced: Cys24Arg and Cys25Tyr mutations abolish mercury resistance, as do charge-substitution mutations in the first predicted transmembrane helix (Gly14Arg, Gly15Arg, Gly27Arg, Ala18Asp), and the termination mutations Trp66Ter and Cys82Ter.
Mol Gen Genet 1996 Jan 15
PMID:Overexpression of MerT, the mercuric ion transport protein of transposon Tn501, and genetic selection of mercury hypersensitivity mutations. 856 83

The neuronal phosphoprotein B-50/GAP-43 is associated with neuronal growth and regeneration and is involved in the calcium/CaM and G(o) signal transduction systems. In particular, B-50 interacts uniquely with CaM by binding in the absence of Ca2+. Previously identified as a major neuronal substrate for protein kinase C, which releases CaM via phosphorylation, B-50 has more recently been shown to be a substrate for endogenous ADP-ribosyltransferases. In the present study, we utilized amino acid modification with iodoacetamide and chemical stability to mercury and neutral hydroxylamine to demonstrate that the predominant site of ADP-ribosylation is Cys 3 and/or Cys 4. Chymotryptic peptide mapping further revealed a second, less labelled site of ribosylation in the C-terminal region. The results also demonstrate that, in contrast to PKC phosphorylation, ADP-ribosylation of B-50 does not mediate CaM binding. Since Cys 3 and Cys 4, by palmitoylation, are important for membrane anchoring, our findings suggest that ADP-ribosylation of B-50 may have a role in directing the intracellular localization of the protein. Hence, ribosylation of B-50 may mediate where B-50 interacts with signal transduction pathways.
Mol Cell Biochem
PMID:Evidence for multisite ADP-ribosylation of neuronal phosphoprotein B-50/GAP-43. 856 28

This study was designed to evaluate the in vitro effects of transition heavy metal cations on activity of constitutive isoform of nitric oxide synthase (cNOS) in rat brain. NOS activity was determined in the cytosolic fractions of rat cerebral hemispheres by conversion of 3H-L-arginine to 3H-L-citrulline. Different concentrations of mercury (Hg2+), nickel (Ni2+), manganese (Mn2+), zinc (Zn2+), cadmium (Cd2+), lead (Pd2+) and calcium (Ca2+) were tested on NOS activity. While all the cations caused inhibition, there were differences in the apparent inhibition constants (Ki) among the cations. With the exception of calcium ion no other cation required preincubation with the enzyme preparation. These results indicate that while calcium ion modulate cNOS activity at regulatory site(s), inhibitory influence of toxic heavy metal cations may be exerted on the catalytic site(s) either by direct binding to it or by interfering with the electron transfer during catalysis.
Mol Cell Biochem
PMID:Interaction of heavy metal toxicants with brain constitutive nitric oxide synthase. 856 38

The complete nucleotide sequence of an 8447 bp-long mercury-resistance transposon (Tn5053) has been determined. Tn5053 is composed of two modules: (i) the mercury-resistance module and (ii) the transposition module. The mercury-resistance module carries a mer operon, merRTPFAD, and appears to be a single-ended relic of a transposon closely related to the classical mercury-resistance transposons Tn21 and Tn501. The transposition module of Tn5053 is bounded by 25 bp terminal inverted repeats and contains four genes involved in transposition, i.e. tniA, tniB, tniQ, and tniR. Transposition of Tn5053 occurs via cointegrate formation mediated by the products of the tniABQ genes, followed by site-specific cointegrate resolution. This is catalysed by the product of the tniR gene at the res region, which is located upstream of tniR. The same pathway of transposition is used by Tn402 (Tn5090) which carries the integron of R751. Transposition genes of Tn5053 and Tn402 are interchangeable. Sequence analysis suggests that Tn5053 and Tn402 are representatives of a new family of transposable elements, which fall into a recently recognized super-family of transposons including retroviruses, insertion sequences of the IS3 family, and transposons Tn552 and Tn7. We suggest that the tni genes were involved in the dissemination of integrons.
Mol Microbiol 1995 Sep
PMID:Four genes, two ends, and a res region are involved in transposition of Tn5053: a paradigm for a novel family of transposons carrying either a mer operon or an integron. 859 37

Little is known at the molecular level concerning the genotoxic effects following the acute exposure of eukaryotic cells to low concentrations of lead (II) or mercury (II). There have been conflicting reports concerning the mutagenic potential of these heavy metals, and there have not been any studies performed to determine the molecular mechanism(s) by which these metals are mutagenic. The Chinese hamster ovary cell line, AS52, contains a stably integrated single functional copy of the Escherichia coli xanthine-guanine phosphoribosyltransferase (gpt) gene. Mutations in the gpt gene confer resistance to 6-thioguanine (TG). There was little effect on viability, as measured by relative cloning efficiency, of AS52 cells exposed to lead (II) or mercury (II) up to concentrations of 0.5 microM and 0.3 microM, respectively. However, higher concentrations of the metals caused a significant increase in cell death. There was also a dose-dependent increase in the isolation of mutants resistant to TG in treated cells when compared to non-treated controls. Concentrations of the metals as low as 0.1 microM caused a significant increase in the number of mutants resistant to TG when compared to the number of spontaneous mutants obtained in nontreated controls. While the molecular mechanism(s) by which lead and mercury (II) are genotoxic is unknown, the results of this study demonstrate that low concentrations of lead (II) and mercury (II) are mutagenic in eukaryotic cells.
Environ Mol Mutagen 1996
PMID:Mutagenesis of AS52 cells by low concentrations of lead(II) and mercury(II) 862 45

The broad-spectrum mercury resistance of Streptomyces lividans 1326 is mediated by six open reading frames (orf). These are arranged in two divergently transcribed operons. The orfs mer A (mercuric reductase) and mer B (organolyase) form one of the two operons. These genes and their regulation were further studied by deletion analysis and transcriptional fusion to the reporter gene xylE in the plasmid pXE4. An increase in XylE activity in response to the presence of mercuric ions was observed. The function of ORF2 (MerT) and ORF3 (MerP) as mercury-specific transport proteins, previously postulated based on the structural features of the predicted proteins, was confirmed. Transcription of the mer genes starts within the intercistronic region and two divergent promoters were identified by S1 nuclease mapping. Expression of the genes was negatively regulated by the product of orf1, now called merR. The repressor function was confirmed by gel retardation assays. MerR, produced in Escherichia coli, bound to two sites (operators) in the fragment containing the promoter region between merA and merR. Addition of mercuric ions and phenylmercuric acetate prevented the binding of MerR.
Mol Gen Genet 1996 Jun 12
PMID:Regulation of the operon responsible for broad-spectrum mercury resistance in Streptomyces lividans 1326. 867 73

Mercury is an element of great pharmacological and toxicological importance. It reacts with sulfhydryl groups on proteins to form mercaptides. Mercuric mercury (Hg2+), a form that shows primarily epithelial toxicity, can inhibit Na+/K(+)-ATPase at low concentration, but its molecular target site on the protein is not known. To investigate the interaction of Hg2+ with Na+/K(+)-ATPase, we studied the inhibition of Na+/K+ pump activity by inorganic mercury (HgCl2) in Xenopus laevis oocytes expressing wild-type and mutant forms of Na+/K(+)-ATPase. Na+/K+ pump potassium-activated current was inhibited with first-order kinetics (Kon = 7 x 10(3) M-1.sec-1) and an estimated Kd of < or = 170 nM. To study the hypothesis that the cysteine (C113) of the first transmembrane segment of the alpha subunit participates in a Hg2+ binding site, we investigated the inhibition of Na+/K+ pump activity produced by a 1-min exposure to 5 microM HgCl2. Wild-type and C113S and C113Y mutant Na+/K+ pumps were inhibited by 43 +/- 7%, 12 +/- 2%, and 5 +/- 3%, respectively. Because C113 is a component of the cardiac steroid binding site, we studied the interaction of mercury with strophanthidin by exposing oocytes for 2 min to 5 microM HgCl2 in the presence or absence of 50 microM strophanthidin. Strophanthidin reduced the inhibition by mercury from 68 +/- 5% to 30 +/- 7%. Based on the position of C113 in the first transmembrane segment, these results suggest that Hg2+ binding to C113 from the extracellular side is one of the mechanisms by which mercury inhibits Na+/K(+)-ATPase.
Mol Pharmacol 1996 Sep
PMID:Mercury binding site on Na+/K(+)-ATPase: a cysteine in the first transmembrane segment. 879 11


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