Protection by lazaroids of the erythrocyte (Ca2+, Mg2+)-ATPase against iron-induced inhibition

Eur J Pharmacol. 1995 Jul 18;290(2):133-9. doi: 10.1016/0922-4106(95)90025-x.

Abstract

The calmodulin-stimulated (Ca2+, Mg2+)-ATPase (calmodulin-ATPase) of the erythrocyte membrane is susceptible to oxidative stress induced by heme and non-heme iron. There is a time-and concentration-dependent inhibition of the calmodulin-ATPase activity when the erythrocyte membranes are treated with either iron or hemin. In the present study, the calmodulin-ATPase has been used as a model system to evaluate the protective effects of a vitamin E analog (U83836E) and two 21-aminosteroids (U74500A and U74389G) against calmodulin-ATPase inhibition induced by iron and hemin. The drugs, lazaroids from Upjohn, can significantly protect the enzyme against iron-induced inhibition and also causes a decrease in the formation of thiobarbituric acid reactive species, with an IC50 of 0.4 microM for the drug U83836E and 4 microM for the drug U74500A. The 21-aminosteroid U74389G does not restore iron-inhibited calmodulin-ATPase activity under similar conditions. At higher concentrations (> 100 microM) all three drugs inhibit the calmodulin-ATPase activity. None of the drugs tested can restore hemin-inhibited calmodulin-ATPase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Ca(2+) Mg(2+)-ATPase / antagonists & inhibitors
  • Ca(2+) Mg(2+)-ATPase / drug effects*
  • Chromans / pharmacology
  • Erythrocytes / drug effects
  • Erythrocytes / enzymology*
  • Humans
  • In Vitro Techniques
  • Iron / antagonists & inhibitors*
  • Iron / pharmacology
  • Lipid Peroxidation / drug effects
  • Piperazines / pharmacology
  • Pregnatrienes / pharmacology

Substances

  • Antioxidants
  • Chromans
  • Piperazines
  • Pregnatrienes
  • U 74389F
  • U 78517F
  • Iron
  • Ca(2+) Mg(2+)-ATPase
  • U 74500A