Induction of stress proteins in rat cardiac myocytes by antimony.
Snawder-JE; Tirmenstein-MA; Mathias-PI; Toraason-M
Toxicol Appl Pharmacol 1999 Sep; 159(2):91-97
The effects of nonlethal concentrations of potassium antimonyl tartrate (PAT) were examined in cultured neonatal rat cardiac myocytes. PAT (5, 10 mM) 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 mM 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 mM) protected against a subsequent lethal concentration of PAT (200 mM). 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.
Antimony-compounds; Myocardium; Myocardial-disorders; Animal-studies; Animals; Laboratory-animals; Laboratory-testing; Cardiac-function; Heart; Potassium-compounds; Stress; Cardiovascular-system-disorders; Cardiopulmonary-system-disorders; Statistical-analysis; Analytical-chemistry; Analytical-methods
Mark Toraason, Cellular Toxicology Section, National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, Ohio 45226
Toxicology and Applied Pharmacology