Effects of calcium channel blockers on stress protein synthesis in cardiac myocytes.
The detection of "stress proteins," certain protein groups of 70 or 30 kDa molecular weight synthesized de novo under stress conditions, serves as an assay for monitoring cellular toxicity. Typical toxins inducing stress protein formation in cardiac myocytes are CdCl2 and H2O2. The synthesis of 68, 71, and 30 kDa stress proteins is evoked by CdCl2, and H2O2 stimulates the formation of a 30 kDa protein. When fetal mouse myocardial cells are incubated first with CdCl2 and then with H2O2 or vice versa, an additive effect on stress protein synthesis can be documented. The calcium antagonists diltiazem, verapamil, and nifedipine, at concentrations above 0.05 mg/ml, stimulate the de novo synthesis of a 30 kDa stress protein. After preincubation of the cardiac myocytes with slow calcium channel blockers, the synthesis of the 70 kDa stress protein family evoked by CdCl2 is reduced. In contrast to the increased stress protein synthesis after heart cells are exposed to toxins, preincubation with calcium antagonists reduces the formation of certain stress proteins. These results indicate an interference of calcium channel blocking drugs with stress protein formation in cultured mouse myocardial cells.
Löw-Friedrich
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I
Department of Nephrology, Hospital of Johann Wolfgang Goethe University, Frankfurt am Main, F.R.G.
Schoeppe
W
W
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D019256:Cadmium Chloride; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002301:Cardiac Glycosides / Q000494:pharmacology; D002478:Cells, Cultured; D004110:Diltiazem / Q000494:pharmacology; D004357:Drug Synergism; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009543:Nifedipine / Q000494:pharmacology; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002301:Cardiac Glycosides; D006360:Heat-Shock Proteins; D002104:Cadmium; D006861:Hydrogen Peroxide; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine; D019256:Cadmium Chloride; D002118:Calcium