Alterations in heart sarcolemmal Ca2+-ATPase and Ca2+-binding activities due to oxygen free radicals

Abstract

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.

Oxidative stress in congestive heart failure

“…In this regard, proteins rich in sulfhydryl groups are highly susceptible to free radical attack [3]. In the myocardium, oxygen radicals have been shown to affect Na + /Ca ++ exchange, Na +-K + , ATPase, and Ca ++ ATPase activities in the sarcolemma [13,14]. Free radicals can also attack the nucleic acids by modifying deoxyribose and base moieties, producing base damage, single strand breaks, and chromosomal aberrations [3,15,16].…”

Oxygen free radicals and calcium homeostasis in the heart

“…We have examined the effects of oxygen free radicals on this ATP-independent CaZ+-binding activity in rat heart sarcolemmal membrane [29]. In the presence of xanthine plus xanthine oxidase or hydrogen peroxide, both low-and highaffinity Ca2+-binding activities were increased after 5 min incubation.…”

The effect of oxygen free radicals on calcium current and dihydropyridine binding sites in guinea‐pig ventricular myocytes

“…The effects of OFRs on L-type calcium current (IC.,L) are not consistent but the majority of the studies describe a decrease in the peak current when myocytes are exposed to an external source of OFRs (Shattock et al, 1990;Cerbai et al, 1991;Tarr & Valenzeno, 1991;Nakaya et al, 1992;Coetzee & Opie, 1992;Gill et al, 1995;Mugelli et al, 1995). The decrease in the current could be due to a direct interaction of OFRs with the L-type Ca-channels or to a Ca-dependent inactivation as a consequence of the increase in intracellular Ca2+ ([Ca2+],) caused by OFRs through different pathways (Kaneko et al, 1990;Shattock et al, 1990;Holmberg et al, 1991;Shattock & Matsuura, 1993).…”