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  • 1
    ISSN: 1432-0738
    Keywords: Methylmercury ; Neurotransmitter ; Enzyme ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The activities of neurotransmitter-metabolizing enzymes were determined in the nervous tissues of rats treated with methylmercury chloride (10 mg/kg/day, for 7 days). The activity of choline acetyltransferase was lowered consistently in the cytosol and synaptosomal fractions of the brain in methylmercury-treated rats, while changes in acetylcholinesterase activity in the brain subcellular fractions were small. In peripheral nerves, decreases in activities of choline acetyltransferase in the sciatic nerve and of acetylcholinesterase in the dorsal root were most profound. Decreases in these enzyme activities started at an early phase and increased markedly with the progress of intoxication. The activity of acetylcholinesterase in the dorsal root ganglion and in the sciatic nerve was also inhibited significantly at the latent period and more profoundly at the symptomatic period at which time crossing of hind limbs, a typical sign of organomercurial poisoning, was observed in the animals. Activities of tyrosine hydroxylase and monoamine oxidase were elevated in the brain homogenate and especially in the synaptosomal fraction with respect to the former enzyme after methylmercury treatment. Effects of methylmercury in vitro on the activities of these enzymes revealed that a much higher amount of methylmercury was required to produce in vitro an inhibitory action equivalent to that observed in vivo. These results suggest that the neurotoxic action of methylmercury could be mediated, at least in part, through the level of neurotransmitter enzymes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein phosphorylation ; Peripheral nerves ; Sciatic nerves ; Myelin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The protein phosphorylation in extracts of nervous tissues of rats acutely exposed to methylmercury chloride (seven daily injections of 10 mg methylmercury chloride/kg body weight) was examined. In the brain, the phosphorylating activity was dependent on cAMP and Mg2+. The effect of methylmercury on the phosphorylation of brain proteins, including tubulin and MAP-2, was hardly discernible. In peripheral nervous tissues such as the dorsal and ventral roots, sciatic nerves and dorsal root ganglia, the phosphorylating activity was dependent on Ca2+, and the maximal activity was obtained when the tissues were extracted in the presence of 1% Triton X−100. SDS-Polyacrylamide gel electrophoresis revealed that the major phosphorylated proteins in the peripheral tissues were myelin proteins. The effects of methylmercury were not uniform regarding protein species and tissues. The most marked changes were observed in sciatic nerves, in which phosphorylation of the 33 kDa, 28 kDa, 19 kDa, 18 kDa and 15 kDa proteins was significantly decreased in the symptomatic phase of intoxication.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein synthesis ; Peripheral nerve ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The in vivo rates of protein synthesis in the peripheral nervous tissues of methylmercury-treated rats (10 mg/kg/day, for 7 days) have been estimated with improved methods by the injection of a large amount of [l-14C]valine of low specific activity. Protein synthesis activity in the dorsal root ganglia was inhibited to the extent of 60% of the control as early as day 5 and this continued to the symptomatic period (day 15) on which crossing of hind limbs, a typical sign of organomercurial poisoning, was observed in the animals. The sciatic nerves and dorsal roots increased protein synthesis by 56% at the symptomatic period. These increases in protein synthesis may be due to the stimulation of reactivity of Schwann's cells. On the contrary, the protein synthesis in the ventral roots showed a gradual decrease as the intoxication proceeded and decreased to 73% of the control at the symptomatic period, being similar to the case of the brain. The double-labeling studies with sodium dodecyl sulfate/polyacrylamide gel electrophoresis exhibited that methylmercury inhibited the synthesis of the dorsal root ganglion proteins non-uniformly in various apparent molecular sizes, especially on day 10.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-0738
    Keywords: Methylmercury ; Aminoacyl tRNA synthetase ; Brain ; Protein synthesis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The activities of six aminoacyl-tRNA synthetase species were determined using enzyme preparations partially purified from the brains of control and methylmercury (MeHg)-treated rats. The activities of Asp-, Leu- and Tyr-tRNA synthetases were significantly reduced in the brains of MeHg-intoxicated rats, whereas those of Lysand Met-tRNA synthetases remained unchanged. In contrast, the activity of His-tRNA synthetase was significantly increased in the symptomatic phase of MeHg intoxication. The activities of these six aminoacyl-tRNA synthetases in the control brains were affected to different extents on the direct addition of MeHg to the assay system in vitro. No positive correlation was observed between the in vivo and in vitro effects of MeHg on the enzyme activities. These results indicate that the aminoacylation of tRNA is one of the actions of MeHg, which leads to inhibition of protein synthesis, and it is suggested that the syntheses of cellular proteins may be modified in different ways by MeHg, depending on their amino acid compositions.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein synthesis ; Liver ; Adrenal ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract (1) A single injection of methylmercury chloride in the rat (10–50 mg/kg) increased both in vivo and in vitro rates of 14C-leucine incorporation into the protein of the post-mitochondrial supernatant fraction of the liver. In contrast, no stimulation of protein synthesis was observed in the brain of the methylmercury-treated rats. (2) Methylmercury administration also stimulated RNA polymerase activities in isolated hepatic nuclei, stimulation of Mg-dependent activity being higher than that of Mn-dependent activity. (3) In experiments with adrenalectomized rats, it was found that the stimulatory effect of methylmercury on protein and RNA synthesis in the liver was mediated partly through the adrenal gland. (4) Analysis of serum by starch-block electrophoresis revealed that synthesis of all serum proteins, including albumin and α-γ globulin fractions, was stimulated by methylmercury treatment. (5) These results suggest that the observed effects of methylmercury on the liver depend on mechanisms other than enhancement of the synthesis of acute-phase proteins.
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Archives of toxicology 56 (1985), S. 236-241 
    ISSN: 1432-0738
    Keywords: Methylmercury ; RNA synthesis ; Dorsal root ganglion ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effect of methylmercury in vivo on the incorporation of 3H-uridine in vitro into RNA of dorsal root ganglia of the rat was examined. Modified methods for the incubation of the tissue and extraction of RNA were applied to adequately determine the rate of RNA synthesis. Methylmercury significantly decreased the RNA content and RNA synthetic activity only in the symptomatic period, while uptake of the precursor into the acid-soluble pool remained unchanged. These results indicate that the previously reported inhibition of protein synthesis in dorsal root ganglia at an early phase of methylmercury intoxication was not due to impairment RNA synthesis in this tissue.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein synthesis ; Dorsal root ganglion ; Two-dimensional electrophoresis ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Dorsal root ganglia from control and methylmercury(MeHg)-treated rats were incubated in vitro with 35S-methionine ant the proteins synthesized were analyzed by two-dimensional electrophoresis. The double labelling method, in which proteins of control dorsal root ganglia labelled in vitro with 3H-leucine were added to each of the two samples as an internal standard, was used to minimize unavoidable errors arising from the resolving procedure itself. The results obtained showed that the effect of MeHg on the synthesis of proteins in dorsal root ganglia was not uniform for individual protein species in the latent period of MeHg intoxication. Among 200 protein species investigated, 157 showed inhibition of synthesis close to that of the total proteins in the tissue (68% of the control). Among the remaining protein species, 20 showed real stimulation of synthesis, whereas 7 were moderately inhibited and 16 were inhibited more strongly than the total proteins in the tissue. These results suggest that the effect of MeHg on the synthetic rates for protein species in dorsal root ganglia differs with the species, and that unusual elevation or reduction of the synthesis of some protein species caused by MeHg may lead to impairment of normal nerve functions.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0738
    Keywords: Methylmercury ; Protein binding ; Peripheral nerves ; Myelin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A small amount of a glycoprotein species (21-kDa glycoprotein) with high affinity for methylmercury (MeHg) was detected in the post-nuclear or post-mitochondrial supernatant fraction of the homogenate of rat sciatic nerve on electrophoresis and autoradiography after binding of Me203Hg to the fraction. The 21-kDa glycoprotein was also found in the subcellular fractions of mouse, hamster, guinea pig, rabbit and human peripheral nervous tissues. Experiments with the cellular fractions of the tissues revealed that the 21-kDa glycoprotein is localized mainly in the myelin fraction, whereas it was not found in the cellular fractions of brain, spinal cord and nonneural tissues, such as kidney and liver. The specific binding activity of the 21-kDa glycoprotein with MeHg was 12–15 fold that of the major myelin protein, Po. It was shown that the interaction of the 21-kDa glycoprotein with MeHg was mediated through sulfhydryl groups in experiments with iodoacetamide and dithiothreitol. The amino acid compositions of the rat and human 21-kDa glycoproteins were similar but very different from that of a typical metallothionein. The N-terminal amino acid sequences of the two components of the rat 21-kDa glycoprotein were identical to those of Po and PMP-22, respectively. The in vitro binding of MeHg was also observed in the myelin fraction obtained from the sciatic nerves of MeHg-dosed rats.
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  • 9
    ISSN: 1432-0738
    Keywords: Methylmercury accumulation ; Biotransformation ; Rat ; Hamster
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The accumulation of mercury in tissues of the rat and hamster was determined after the administration of a single dose of 203Hg-methylmercury chloride (10mg/kg body weight). (1) On day 2, the mercury contents of hamster tissues were higher than those of rat tissues, except for red blood cells, in which the mercury content was about 6-fold higher in the rat than in the hamster. (2) After that time, the mercury content of hamster tissues decreased rather steeply and on day 16 it had reached 14–25% in nervous tissues and 7–15% in other tissues, of the levels on day 2. (3) In the rat, on the other hand, the mercury content of nervous tissues on day 16 was higher than that on day 2 (106–220%), except for dorsal roots and dorsal root ganglia, which showed slight decreases (75–94% of the levels on day 2). In non-neural tissues, the decreases up to day 16 were also small (71–92% of the levels on day 2). (4) Thus, both the uptake and elimination of mercury seem to be more rapid in the tissues of hamster compared with those of the rat. Similar trends of mercury accumulation and elimination were observed when animals received multiple injections of methylmercury that induced acute methylmercury intoxication. (5) Significant biotransformation of the injected methylmercury to inorganic mercury was detected in the liver, kidney and spleen of both animal species. Although the percentages of inorganic mercury in these tissues were not so different between the two species on day 2, they became exceedingly high in the tissues of hamster at the later stage, except in the kidney cytosol, in which the values were close in both animal species between day 2 and day 16.
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  • 10
    ISSN: 1432-0738
    Keywords: Methylmercury ; Inorganic mercury ; Rat ; Subcellular distribution ; Biotransformation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Accumulation of inorganic mercury in subcellular fractions of the kidney, liver, and brain of rats was studied during 48 days after a single injection of 25 mg/kg of methylmercury chloride. The highest ratio of inorganic to total mercury was seen in the cytosol of kidney, 80% of the total being as inorganic mercury at day 48. The ratio in the mitochondria and microsomes of kidney attained a maximum level (about 50% of the total as inorganic) at day 26–37. In the liver, the ratio was strikingly low in the cytosol and microsomes as compared to the light and heavy mitochondria where about 40% of the total was present as inorganic maximally at day 26. The ratio in the brain, determined up to day 15, was very low as compared with the kidney and liver, showing less than 3% of the total in the mitochondria, microsomes, and cytosol, and 5.4% in the myelin fraction. The high accumulation of inorganic mercury in the cytosol of kidney was closely related to metallothionein-like component, while those in the mitochondria and microsomes of kidney and in the mitochondria of liver were exclusively bound to high molecular weight proteins even after deoxycholate treatment.
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