Induction of stress proteins in rat cardiac myocytes by antimony.
The effects of nonlethal concentrations of potassium antimonyl tartrate (PAT) were examined in cultured neonatal rat cardiac myocytes. PAT (5, 10 microM) significantly increased cellular reduced glutathione (GSH) and heme oxygenase activity after 18 h. GSH levels and heme oxygenase activity were increased 2.5- and 5.4-fold, respectively, by 10 microM PAT after 18 h. In addition, total cytochrome P450 levels were decreased by PAT after an 18-h exposure. PAT exposures were associated with the induction of specific stress proteins. Nonlethal concentrations of PAT produced a dose-dependent increase in HO-1, HSP70, and HSP25/27 protein levels but did not increase HSP60 levels. Pretreatment of cardiac myocytes with low concentrations of PAT (0.5-10 microM) protected against a subsequent lethal concentration of PAT (200 microM). This protection was blocked if cells were treated with the protein synthesis inhibitor cycloheximide. Results demonstrate that low concentrations of PAT increase GSH levels and stress protein synthesis, which may be responsible for the protection that low-level PAT exposure offers against the subsequent toxicity of higher concentrations of PAT.
Snawder
J E
JE
Cellular Toxicology Section, National Institute for Occupational Safety and Health, Cincinnati, Ohio 45226, USA.
Tirmenstein
M A
MA
Mathias
P I
PI
Toraason
M
M
D000818:Animals; D000831:Animals, Newborn; D000966:Antimony Potassium Tartrate / Q000633:toxicity*; D015153:Blotting, Western; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D007150:Immunohistochemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D003577:Cytochrome P-450 Enzyme System; D003513:Cycloheximide; D000966:Antimony Potassium Tartrate; D006419:Heme Oxygenase (Decyclizing); D005978:Glutathione