Protective elevations of glutathione and metallothionein in cadmium-exposed mesangial cells.
Exposure of cultured rat mesangial cells to CdCl2 caused a dose- and time-dependent increase in intracellular glutathione that was significant at 0.5 microM and maximal at 1 microM Cd2+. The effect depended on glutathione synthesis and was masked by inhibiting synthesis with buthionine sulfoximine. The cells responded to slightly higher concentrations of Cd with a marked decrease in DNA synthesis, and reversible depletion of glutathione enhanced this sensitivity. Pre-induction of the thiol-rich protein metallothionein with ZnCl2 afforded a degree of protection to the glutathione-depleted cells. We conclude that the Cd-dependent elevation of glutathione in these cells may be protective at concentrations of Cd that can arise during acute environmental and occupational exposures.
Chin
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Department of Clinical Biochemistry, University of Toronto, Canada.
Templeton
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D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D019328:Buthionine Sulfoximine; D002104:Cadmium / Q000633:toxicity*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005920:Glomerular Mesangium / Q000737:chemistry* / Q000166:cytology / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis*; D008297:Male; D008668:Metallothionein / Q000032:analysis*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D015032:Zinc / Q000494:pharmacology
D000963:Antimetabolites; D002104:Cadmium; D014316:Tritium; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D004247:DNA; D008668:Metallothionein; D005978:Glutathione; D015032:Zinc; D013936:Thymidine