title: Alterations in renal cellular glutathione metabolism after in vivo administration of a subtoxic dose of mercuric chloride.
abstract: Renal cellular concentration of glutathione (GSH) increases after exposure to a subtoxic dose of inorganic mercury (Hg2+). In the present study, we tested the hypothesis that the increase in renal cellular concentration of GSH after exposure to a subtoxic dose of Hg2+ (0.5 mumol HgCl2/kg body wt) is due to induction of GSH synthesis. Rats were treated in vivo with HgCl2, and renal proximal tubular (PT) and distal tubular (DT) cells were isolated 24 hours later. PT cells were studied as the presumed target site for Hg2+, and DT cells were investigated as a nontarget cell population. gamma-Glutamylcysteine synthetase activity increased after exposure to Hg2+ in PT cells when expressed on a per cell basis. Increases in activities of glutathione disulfide (GSSG) reductase, GSH peroxidase, and several enzymes involved in cellular energetics occurred after exposure to Hg2+. Many of these increases were observed in both PT and DT cells, indicating that the responses to Hg2+ were not restricted to the PT cells. These results are consistent with the hypothesis that in vivo exposure to a subtoxic dose of Hg2+ is also associated with induction of GSH synthesis and other key cellular enzymes. Early changes in GSH metabolism associated with exposure to Hg2+ appear to occur both in the primary target cell population and in more distal nephron sites.
authors.affiliation: Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201, USA. LHLASH@cms.cc.wayne.edu.
authors.forename: L H
authors.initials: LH
authors.lastname: Lash
authors.forename: R K
authors.initials: RK
authors.lastname: Zalups
mesh_terms: D000818:Animals; D004247:DNA / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives / Q000378:metabolism*; D019803:Glutathione Disulfide; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D009399:Nephrons / Q000166:cytology / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D011506:Proteins; D008627:Mercuric Chloride; D004247:DNA; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005721:Glutamate-Cysteine Ligase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D019803:Glutathione Disulfide