Glutathione, albumin, cysteine, and cys-gly effects on toxicity and accumulation of mercuric chloride in LLC-PK1 cells.
Speciation plays a profound if not dominant role in both transport and toxicity of Hg(II). Hg(II) has a high affinity for sulfhydryl groups. The formation constant for Hg2+ and the anionic form of a sulfhydryl group R-S- is > or =10(10) higher than that for the carboxyl or amino groups. The kidneys are the target organ for Hg(II) toxicity and the primary site of Hg(II) accumulation. Sulfhydryl groups have been implicated in both transport and nephrotoxicity; however, the role endogenous thiol compounds play in these parameters is not clear. The roles that albumin, glutathione, and the glutathione-derived complexes cysteinylglycine and L-cysteine play in toxicity and accumulation of HgCl2 were studied in LLC-PK1 cells incubated with different Hg(II):thiol ratios. In cysteine-containing medium, almost all 1:2 Hg(II):thiol complexes protected against Hg(II) toxicity up to 120 microM Hg, increased membrane-bound Hg(II), and decreased intracellular Hg(II) accumulation. In cysteine-free medium, all 1:1 Hg(II):thiol complexes were as toxic as uncomplexed Hg(II), and almost all 1:2 Hg(II):thiol complexes protected at > or =20 microM Hg, except albumin, which protected at < or =20 microM Hg. In cysteine-free but cystine-containing medium, two 1:1 Hg(II):thiol complexes were toxic at > or =80 microM Hg and two provided complete protection. All 1:2 complexes provided protection at 80-160 microM Hg. This investigation used defined media to demonstrate that mercury cytotoxicity in LLC-PK1 cells was dependent on Hg(II) concentration, the ligand, and the presence of a cysteine source for the cells. These effects were only partially explained by intracellular Hg(II) levels.
Divine
K K
KK
Department of Pharmacology and Toxicology, Center for Toxicology, College of Pharmacy, University of Arizona, Tucson 85721, USA.
Ayala-Fierro
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F
Barber
D S
DS
Carter
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DE
D000418:Albumins / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D003545:Cysteine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000378:metabolism; D007668:Kidney / Q000166:cytology / Q000187:drug effects*; D018374:LLC-PK1 Cells / Q000187:drug effects*; D008627:Mercuric Chloride / Q000633:toxicity*; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013552:Swine
D000418:Albumins; D004151:Dipeptides; D004785:Environmental Pollutants; D013438:Sulfhydryl Compounds; C028505:cysteinylglycine; D008627:Mercuric Chloride; D005978:Glutathione; D003545:Cysteine