Intracellular glutathione (GSH) levels modulate mercuric chloride (MC)- and methylmercuric chloride (MeHgCl)-induced amino acid release from neonatal rat primary astrocytes cultures.
Mercuric chloride (MC) and methylmercury (MeHg) were found to increase amino acid release from astrocytes. This suggests interaction with sulfhydryl (-SH) groups which are controlled by glutathione [GSH] levels. In the present study, we evaluated the effects of alterations in intracellular glutathione concentrations [GSH]i on the outcome of MC and MeHg treatment. [GSH]i were increased in a time-dependent fashion by incubating the astrocytes with 1 mM L-2-oxothiazolidine-4-carboxylic acid (OTC), a cysteine precursor. OTC attenuated the release of [2,3-3H]D-aspartic acid from astrocytes exposed to MC- (5 microM) and MeHg-(10 microM). MeHg-induced [3H]D-taurine release was also reduced by pretreatment of astrocytes with OTC. Treatment with BSO (50 microM) decreased [GSH]i in astrocytes, and increased [2,3-3H]D-aspartate release from MC- and MeHg-treated astrocytes, and [3H]D-taurine release from MeHg-treated cells. Neither OTC nor BSO when added to cultures in the absence of MC or MeHg had an effect on amino acid release by astrocytes. The current study underscores both the sensitivity of astrocytes to mercurials in terms of amino acid release and the relationship of these effects of astrocytic [GSH]i.
Aschner
M
M
Department of Pharmacology and Toxicology, Albany Medical College, NY.
Mullaney
K J
KJ
Wagoner
D
D
Lash
L H
LH
Kimelberg
H K
HK
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D005721:Glutamate-Cysteine Ligase / Q000037:antagonists & inhibitors; D005978:Glutathione / Q000378:metabolism*; D008627:Mercuric Chloride / Q000494:pharmacology*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D008767:Methylmercury Compounds / Q000494:pharmacology*; D011761:Pyrrolidonecarboxylic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D013654:Taurine / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D053778:Thiazolidines; D014316:Tritium
D008767:Methylmercury Compounds; D013844:Thiazoles; D053778:Thiazolidines; D014316:Tritium; D008717:Methionine Sulfoximine; D013654:Taurine; D001224:Aspartic Acid; D019328:Buthionine Sulfoximine; D008627:Mercuric Chloride; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; C004925:methylmercuric chloride; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid