In vivo effect of methylmercury on protein synthesis in brain and liver of the rat

Omata, Saburo; Sakimura, Kenji; Tsubaki, Hidemi; Sugano, Hiroshi

doi:10.1016/0041-008x(78)90197-7

Cited by 65 publications

(13 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6, together with log Krc for the CH3Hg(II) complexes of glutathione (GSH). Glutathione is the most abundant nonprotein thiol in biological systems (I8), and has been identified as CH3Hg(II) binding site in red blood cells (3,19) and liver cytosol (20), and 30% of rat cerebral soluble CH3Hg(II) is in a GSH complex (21). The curves illustrate the complexity of the situation, since at high dithiol:CH,Hg(II) ratios such as those expected under antidotal conditions, log Kfc(DMPS) > log K,(DMSA) > log Krc(GSH) but at low ratios the order is altered to log Krc(DMSA) > log K,(GSH) > log K,(DMPS).…”

mentioning

confidence: 99%

Nuclear magnetic resonance and potentiometric studies of the complexation of methylmercury(II) by dithiols

Arnold¹,

Canty²,

Reid³

et al. 1985

Can. J. Chem.

View full text Add to dashboard Cite

. Can. J. Chem. 63, 2430Chem. 63, (1985. Complexation of methylmercury, CH3Hg(II), by 2,3-dimercaptosuccinic acid (DMSA), 2,3-dimercaptopropanesulfonate (DMPS, Unithiol), dithioerythritol (DTE), and 2,3-dimercaptopropanol (British AntiLewisite, BAL) has been studied by 'H nuclear magnetic resonance spectroscopy and by potentiometric titration. In the nmr study, the equilibrium constants for displacement of mercaptoacetate from its CH3Hg(II) complex by the dithiols were determined over a wide pH range, from mercaptoacetate chemical shift data. Similar competition reactions between the dithiols and mercaptoethanol were used in the potentiometric study. Using previously determined CH3Hg(II) formation constants for the competing ligands, equilibrium constants for the formation of mono-and bis-CH3Hg(II) complexes with the dithiols have been determined. The formation constants for the mono-CH3Hg(II) complexes with the vicinal dithiols BAL and DMPS are significantly higher than expected by consideration of the basicity of the sulfhydryl donors, in comparison with those for DMSA, non-vicinal DTE, and monothiols. We interpret this to indicate chelation of CH3Hg(II) by BAL and DMPS but not by DMSA. The conditional formation constants at physiological pH are discussed with reference to the effectiveness of BAL, DMPS, and DMSA as antidotes for methylmercury poisoning. In particular, the constants obtained indicate that, for dithiol antidotes at concentrations greater than that of methylmercury(II), methylmercury(I1) complexes formed at physiological pH are of 1 : 1 stoichiometry. For BAL, a substantial proportion of the complex will be in the neutral form, in contrast to DMPS and DMSA which form anionic species only. Faisant appel 21 la rmn du 'H et i des titrages potentiomCtriques, on a CtudiC la complexation du mCthylmercure, CH3Hg(II), par les composCs suivantes: I'acide dimercaptosuccinique (ADMS), le dimercapto-2,3 propanesulfonate (DMPS, Unithiol), le dithioCrythritol (DTE) et le dimercapto-2,3 propanol (British AntiLewisite, BAL). A partir des donntes de dkplacement chimique du mercaptoacetate en rmn du 'H, on a determine, sur un large intervalle de pH, les constantes d'Cquilibre des rkactions de dCplacement, par les dithiols, du mercaptoacCtate de son complexe de CH3Hg(II). On a Cgalement utilisC des rkactions de compCtitions du mCme type entre des dithiols et le mercaptoCthanol, lors de 1'Ctude potentiomktrique. Faisant appel a des constantes de formation du CH3Hg(II) qui ont Ct C dCterminCes anterieurement pour les ligands entrant en competition, on a dCterminC les constantes dlCquilibre de formation des complexes mono-et bis-CH3Hg avec les dithiols. Si on les compare avec les constantes de I'ADMS, du DTE (qui sont des dithiols qui ne sont pas vicinaux) ou avec celles des monothiols, les constantes de formation des complexes de mono-CH3Hg(II) avec les dithiols vicinaux BAL et DMPS sont nettement plus ClevCes que celles prCvues en tenant compte de la basicit6 des sulfhydryles donneurs. Pour interprkter ces rCsult...

show abstract

mentioning

confidence: 99%

Nuclear magnetic resonance and potentiometric studies of the complexation of methylmercury(II) by dithiols

Arnold¹,

Canty²,

Reid³

et al. 1985

Can. J. Chem.

View full text Add to dashboard Cite

show abstract

“…Day 1 means the day on which the first injection was given. Evolution of methylmercury intoxication in the rats was as described in our previous paper (Omata et al 1978). Day 15 corresponds to the symptomatic phase,…”

Section: Methodsmentioning

confidence: 99%

“…Animals of the two sub-groups were killed on days 10 and 15, respectively. Whole-body perfusion was carried out as described previously (Omata et al 1978). Tissues from three rats were pooled, weighed, and homogenized with a medium containing 20 mM HEPES buffer, pH 7.6, 25 mM KCI, 10 mM MgCl2, and 0.25 M sucrose.…”

Section: Accumulation Of Mercury In the Tissuesmentioning

confidence: 99%

“…From the point of view that defect of protein synthesis in the nervous system may have a deep correlation to the toxic effects of methylmercury (Brown and Yoshida 1965;Miyakawa and Deshimaru 1969;Chang and Hartmann 1972;Klein et al 1972), several studies have been carried out to date to show that Send offprint requests to S. Omata at the above address * This work was supported in part by a grant from the Japanese Environmental Agency and by the Grant-in-Aid for Scientific Research from the Ministry of Education of Japan methylmercury could produce a disturbance to protein synthesis activity in the rat brain (Yoshino et al 1966;Cavanagh and Chen 1971a;Farris and Smith 1975;Verity et al 1977;Syversen 1977;Omata et al 1978Omata et al , 1980a. On the other hand, when methylmercury compounds are given to rats, there is both morphological and functional evidence that the primary site of action of methylmercury is in the peripheral nerves (Hunter et al 1940;Miyakawa et al 1970;Cavanagh and Chen 1971b;Chang and Hartmann 1972b;Klein et al 1972;Herman et al 1973;Somjen et al 1973a;Jacobs et al 1975).…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

In vivo effect of methylmercury on protein synthesis in peripheral nervous tissues of the rat

et al. 1982

Self Cite

View full text Add to dashboard Cite

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 [1-14C]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 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.

show abstract

“…In the experiment in which the binding of MeHg to the sciatic nerve proteins of MeHg-dosed rats was examined, MeHg as methylmercury chloride (10 mg/kg/day) was administered to rats subcutaneously for 7 consecutive days, as described previously (Omata et al 1978). Control rats, which received seven injections of the vehicle alone, were killed 7 days after the last injection.…”

Section: Animal Treatmentmentioning

confidence: 99%

Identification and partial characterization of a glycoprotein species with high affinity for methylmercury in peripheral nervous tissues of man and experimental animals

et al. 1993

Self Cite

View full text Add to dashboard Cite

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 P0 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.

show abstract

In vivo effect of methylmercury on protein synthesis in brain and liver of the rat

Cited by 65 publications

References 7 publications

Nuclear magnetic resonance and potentiometric studies of the complexation of methylmercury(II) by dithiols

Nuclear magnetic resonance and potentiometric studies of the complexation of methylmercury(II) by dithiols

In vivo effect of methylmercury on protein synthesis in peripheral nervous tissues of the rat

Identification and partial characterization of a glycoprotein species with high affinity for methylmercury in peripheral nervous tissues of man and experimental animals

Contact Info

Product

Resources

About