Effect of amino acids on brain uptake of methyl mercury

Hirayama, Kazutsugu

doi:10.1016/0041-008x(80)90093-9

Cited by 69 publications

(36 citation statements)

References 11 publications

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“…In particular, co-administration of Cys with CH 3 Hg + has been shown to increase the uptake of CH 3 Hg + into capillary endothelial cells of the blood-brain barrier. Interestingly, experiments in rats demonstrated that the uptake of CH 3 Hg + is inhibited significantly by the neutral amino acid, phenylalanine (Hirayama, 1980(Hirayama, , 1985Thomas and Smith, 1982). The data from these experiments led to the hypothesis that the Cys S-conjugate of CH 3 Hg + (CH 3 Hg-SCys) is a transportable substrate of a neutral amino acid transporter in the capillary endothelium of the blood-brain barrier.…”

Section: Molecular Mimicry and The Transport Of Ch 3 Hg + In Brainmentioning

confidence: 92%

“…In fact, initial studies utilizing homogenates of rat cerebrum demonstrated that the primary non-protein thiol bound to CH 3 Hg + is GSH (Thomas and Smith, 1979). Subsequent studies in rats and primary cultures of bovine brain endothelial cells revealed a possible role for Cys in the transport of CH 3 Hg + across the blood-brain barrier (Hirayama, 1980;Clarkson, 1988, 1989). In particular, co-administration of Cys with CH 3 Hg + has been shown to increase the uptake of CH 3 Hg + into capillary endothelial cells of the blood-brain barrier.…”

Section: Molecular Mimicry and The Transport Of Ch 3 Hg + In Brainmentioning

confidence: 99%

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Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

677

460

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Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

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Section: Molecular Mimicry and The Transport Of Ch 3 Hg + In Brainmentioning

confidence: 92%

Section: Molecular Mimicry and The Transport Of Ch 3 Hg + In Brainmentioning

confidence: 99%

Molecular and ionic mimicry and the transport of toxic metals

Bridges

Zalups

2005

Toxicology and Applied Pharmacology

677

460

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“…3,4) In addition, it also has been suggested that the more efficient transport activity of neutral amino acids into the brain in LPD-fed mice than in NPDfed mice would contribute to the higher brain Hg concentration, 7,10,11) since MeHg is transported into the brain as its L-cysteine conjugate through the neutral amino acid transport system. [12][13][14][15][16][17] Furthermore, we showed that treatment with acivicin, a specific inhibitor of γ-glutamyltranspeptidase (γ-GTP), 18,19) markedly promoted urinary Hg excretion and resulted in similar excretion in the two dietary groups. 6) Since this suggested that the influx rates of low molecular weight (LMW) MeHg metabolites into the proximal luminal space, through glomerular filtration and through the secretion system for GSH and its S-conjugates, 4,20) would be similar in the two dietary groups, 6) we assumed that the marked decrease in urinary Hg excretion by the lowered dietary protein level might be caused by efficient re-absorption of MeHg metabolites such as MeHg-Lcysteine from the proximal luminal space.…”

Section: Introductionmentioning

confidence: 84%

Influence of Dietary Protein Levels on the Fate of Methylmercury and on Amino Acid Transport at the Renal Brush Border Membrane in Rats

Adachi

Hirayama

2005

JOURNAL OF HEALTH SCIENCE

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We investigated the influence of dietary protein levels on the fate of methylmercury (MeHg) in rats, and the difference in its urinary excretion was discussed from the viewpoint of the dietary protein level-dependent alteration in activity of the neutral amino acid transport system, through which MeHg metabolites such as MeHg-L-cysteine are reabsorbed, at the renal brush border membrane. When MeHg was administered to rats fed either a 24.8% protein diet (normal protein diet, NPD) or a 7.5% protein diet (low protein diet, LPD), urinary Hg excretion was much lower in LPD-fed rats than in NPD-fed rats, whereas no difference was observed in fecal excretion 1 day after MeHg administration. At that time, Hg concentrations in the brain and plasma were similar in the two dietary groups, whereas the concentrations in liver and blood were higher, but the renal concentration was lower in LPD-fed rats than in NPD-fed rats. Regardless of the presence of Na + , uptake of 14 C-L-phenylalanine for the first 20 sec was higher in the renal brush border vehicles from LPD-fed rats than in those from NPD-fed rats. These results suggest that dietary protein deficiency enhances the neutral amino acid transport at the renal brush border membrane, which could lead efficient reabsorption of MeHg metabolites from the proximal luminal space, and it might play a key role in the marked decrease in urinary excretion of MeHg.

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“…Methylmercury (MeHg) is easily absorbed from the gastrointestinal tract of mammals, and it easily passes through the blood-brain barrier and placental barrier via the transport system for neutral amino acids, to be distributed to nervous tissues and a fetus if one is present (Hirayama, 1980(Hirayama, , 1985Aschner and Clarkson, 1988;Kajiwara et al, 1996). The neuronal toxicity and fetal toxicity of MeHg are well documented in experimental animals and humans (Choi, 1989;Clarkson, 1997;Clarkson et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Demethylation of methylmercury and the enhanced production of formaldehyde in mouse liver

Uchikawa

Kanno²,

Maruyama³

et al. 2016

J. Toxicol. Sci.

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-Methylmercury (MeHg) is gradually changed to inorganic Hg after demethylation in animal tissues, and a selective quantification of inorganic Hg in the tissues is necessary to detect the reaction. We detected inorganic Hg formation in liver and kidney of mouse as early as 24 hr after MeHg injection. As an example of biological demethylation, the cytochrome P450 (P450)-mediated N-demethylation of drugs has been well documented, and formaldehyde was detected as a reaction product. Here we incubated mouse liver homogenate with added MeHg and observed a dose-dependent production of formaldehyde, as well as inorganic Hg formation. Since the amount of formaldehyde was approx. 500 times higher than that of the inorganic Hg that formed, the formaldehyde production would be stimulated by inorganic Hg formed from MeHg. We observed that inorganic Hg caused formaldehyde production, and it was enhanced by L-methionine and sarcosine. Thus, some biomolecules with S-methyl and N-methyl groups may function as methyl donors in the reaction. Using subcellular fractions of mouse liver, we observed that microsomal P450 did not participate in the demethylation of MeHg, but the greatest activity was located in the mitochondria-rich fraction. The addition of superoxide anion in the reaction mixture significantly enhanced the formaldehyde production, whereas Mn-superoxide dismutase depressed the reaction. Our present findings demonstrated that inorganic Hg formed by MeHg demethylation in mouse liver stimulated the endogenous formaldehyde production, and we observed that MeHg demethylation could be estimated by a formaldehyde analysis. Our results also suggested that superoxide anion is involved in the reaction.

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Effect of amino acids on brain uptake of methyl mercury

Cited by 69 publications

References 11 publications

Molecular and ionic mimicry and the transport of toxic metals

Molecular and ionic mimicry and the transport of toxic metals

Influence of Dietary Protein Levels on the Fate of Methylmercury and on Amino Acid Transport at the Renal Brush Border Membrane in Rats

Demethylation of methylmercury and the enhanced production of formaldehyde in mouse liver

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