Methylmercury Efflux from Brain Capillary Endothelial Cells Is Modulated by Intracellular Glutathione but Not ATP

To reach its target tissue, methylmercury must traverse brain capillary endothelial cells, the site of the blood–brain barrier. Methylmercury uptake from blood plasma into these cells is mediated in part by an amino acid carrier that transports the methylmercury–L-cysteine complex; however, the mech...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 1996-12, Vol.141 (2), p.526-531
Main Authors: Kerper, Laura E., Mokrzan, Elaine M., Clarkson, Thomas W., Ballatori, Nazzareno
Format: Article
Language:English
Subjects:
Adenosine Triphosphate - physiology
Animals
Biological and medical sciences
Brain - blood supply
Capillaries - metabolism
Cattle
Cells, Cultured
Chemical and industrial products toxicology. Toxic occupational diseases
Endothelium, Vascular - metabolism
Glutathione - physiology
Medical sciences
Metals and various inorganic compounds
Methylmercury Compounds - pharmacokinetics
Space life sciences
Toxicology
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Summary:To reach its target tissue, methylmercury must traverse brain capillary endothelial cells, the site of the blood–brain barrier. Methylmercury uptake from blood plasma into these cells is mediated in part by an amino acid carrier that transports the methylmercury–L-cysteine complex; however, the mechanism by which it is released from the endothelial cells into brain interstitial space is unknown. Using bovine brain capillary endothelial cells in culture, the present study examined the hypothesis that methylmercury is transported out of these cells as a glutathione (GSH) complex. GSH concentration in cultured bovine brain capillary endothelial cells was 13.1 ± 3.3 nmol/mg protein. Depletion of intracellular GSH in [203Hg]methylmercury-preloaded cells by exposure to 1-chloro-2,4-dinitrobenzene or diethyl maleate decreased the rate of [203Hg]methylmercury efflux. Incubation of [203Hg]methylmercury-preloaded cells with high concentrations ofS-methylglutathione,S-ethylglutathione,S-butylglutathione, and sulfobromophthalein–glutathione inhibited [203Hg]methylmercury efflux. The GSH analogs γ-glutamylglycylglycine and ophthalmic acid also inhibited [203Hg]methylmercury efflux, but to a lesser degree than the glutathioneS-conjugates, whereasL-leucine,L-methionine, andL-alanine had no effect. Efflux was not affected by depletion of intracellular ATP with 2-deoxyglucose or antimycin A. These results indicate that complexation with GSH and subsequent transport of the complex by an ATP-independent mechanism may be involved in the transport of methylmercury out of brain capillary endothelial cells.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.1996.0318