Mechanism for depression of heart sarcolemmal Ca2+ pump by oxygen free radicals.
To understand the involvement of changes in sulfhydryl groups in causing depression of the sarcolemmal Ca2+-pump activities, this study was undertaken to examine the effects of oxygen free radicals on rat heart sarcolemmal sulfhydryl groups, Ca2+-stimulated adenosinetriphosphatase (ATPase), and ATP-dependent Ca2+ accumulation. In addition, the effects of sulfhydryl reagents such as dithiothreitol, cysteine, and N-ethylmaleimide on Ca2+-pump activities were investigated. The inhibition of sarcolemmal Ca2+-pump activities by O2-. (xanthine + xanthine oxidase) and H2O2 was decreased by the addition of dithiothreitol or cysteine in a dose-dependent manner. N-ethylmaleimide also showed inhibitory effects on Ca2+-pump activities both in a dose- and time-dependent manner; dithiothreitol and cysteine prevented changes in Ca2+-pump activities because of N-ethylmaleimide. Heart sarcolemmal sulfhydryl groups were depressed by O2-., H2O2, and .OH (H2O2 + Fe2+) both in a dose- and time-dependent manner. Superoxide dismutase, catalase, and D-mannitol showed protective effects on the sulfhydryl group depression by O2-., H2O2, and .OH, respectively. A significant correlation between changes in sarcolemmal Ca2+-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen. These results indicate that oxygen free radicals may depress the heart sarcolemmal Ca2+-pump activities by modifying the sulfhydryl groups in the sarcolemmal membrane.
Kaneko
M
M
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Elimban
V
V
Dhalla
N S
NS
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D005609:Free Radicals; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000648:ultrastructure; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000378:metabolism*; D013439:Sulfhydryl Reagents / Q000494:pharmacology; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D015220:Calcium Channels; D005609:Free Radicals; D013439:Sulfhydryl Reagents; D014970:Xanthines; D019820:Xanthine; D000255:Adenosine Triphosphate; D014969:Xanthine Oxidase; D000251:Adenosine Triphosphatases; D010100:Oxygen; D002118:Calcium