Alterations in heart sarcolemmal Ca2(+)-ATPase and Ca2(+)-binding activities due to oxygen free radicals.
Effects of oxygen free radicals on Ca2+/Mg2+ ATPase and ATP-independent Ca2(+)-binding activities were examined in rat heart sarcolemma. Membranes were incubated with different oxygen radical generating media such as xanthine + xanthine oxidase, hydrogen peroxide, and hydrogen peroxide + Fe2+. In the presence of xanthine + xanthine oxidase, Ca2+ ATPase activity was stimulated and this effect was prevented by the addition of superoxide dismutase. Hydrogen peroxide also showed a significant increase in Ca2(+)-ATPase activity in a dose-dependent manner and this effect was blocked by catalase. On the other hand, a combination of hydrogen peroxide + Fe2+ decreased Ca2(+)-ATPase activity; this depression was prevented by the addition of D-mannitol. The observed change in Ca2(+)-ATPase activity due to oxygen free radicals was associated with changes in Vmax, whereas Ka remained unaffected. Both xanthine + xanthine oxidase and hydrogen peroxide increased whereas, hydrogen peroxide + Fe2+ inhibited the ATP-independent Ca2(+)-binding activities. It is suggested that oxygen free radicals may influence Ca2+ movements in the cell by altering the Ca2+/Mg2+ ATPase and Ca2(+)-binding activities of the membrane and these effects may be oxygen-radical species specific.
Kaneko
M
M
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Singal
P K
PK
Dhalla
N S
NS
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006878:Hydroxides / Q000378:metabolism*; D017665:Hydroxyl Radical; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D010101:Oxygen Consumption / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012508:Sarcolemma / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism*; D019820:Xanthine; D014969:Xanthine Oxidase / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D005609:Free Radicals; D006878:Hydroxides; D014970:Xanthines; D013481:Superoxides; D019820:Xanthine; D017665:Hydroxyl Radical; D006861:Hydrogen Peroxide; D014969:Xanthine Oxidase; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases