Inhibition of heart sarcolemmal Ca(2+)-pump activity by oxygen free radicals

Bratisl Lek Listy. 1991 Jan;92(1):48-56.

Abstract

Oxygen free radicals have been implicated as mediators of cellular injury in ischemia-reperfusion. Since intracellular Ca(2+)-overload has been considered to play a crucial role in ischemia-reperfusion injury, this study was undertaken to examine the effects of oxygen free radicals on Ca(2+)-stimulated Mg(2+)-dependent ATPase activities and ATP-dependent Ca2+ accumulation in rat cardiac sarcolemmal membranes in vitro. Isolated rat heart sarcolemmal membranes were incubated with xanthine (X) + xanthine oxidase (XO) and assayed for Ca(2+)-pump activities. X + XO inhibited the Ca(2+)-pump activities in a time-dependent manner; a significant inhibition of Ca(2+)-stimulated ATPase activity was seen after one min of incubation. Superoxide dismutase showed a protective effect on depression in Ca(2+)-pump activities due to X + XO. To understand the involvement of sulfhydryl groups changes in causing depression of Ca(2+)-pump activities, the effects of oxygen free radicals on heart sarcolemmal sulfhydryl groups were also investigated. Heart sarcolemmal sulfhydryl groups were decreased by X + XO in a time-dependent manner. Superoxide dismutase showed a protective effect on sulfhydryl group depression caused by X + XO. N-ethylmaleimide, a sulfhydryl reagent, showed inhibitory effect on Ca(2+)-pump activities both in a time-, and a dose-dependent manner; dithiothreitol and cysteine prevented changes in Ca(2+)-pump activities caused by N-ethylmaleimide. The inhibitory effect of X + XO on Ca(2+)-pump activities were also prevented by the addition of dithiothreitol or cysteine. A significant correlation between changes in sarcolemmal Ca(2+)-stimulated ATPase activity and sarcolemmal sulfhydryl groups was seen.(ABSTRACT TRUNCATED AT 250 WORDS)

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Biological Transport, Active
  • Calcium / metabolism*
  • Female
  • Free Radicals*
  • In Vitro Techniques
  • Myocardium / metabolism*
  • Myocardium / ultrastructure
  • Rats
  • Rats, Inbred Strains
  • Sarcolemma / metabolism*
  • Sulfhydryl Compounds / metabolism
  • Xanthine
  • Xanthine Oxidase / pharmacology
  • Xanthines / pharmacology

Substances

  • Free Radicals
  • Sulfhydryl Compounds
  • Xanthines
  • Xanthine
  • Adenosine Triphosphate
  • Xanthine Oxidase
  • Calcium