Inhibition of the erythrocyte (Ca2+ + Mg2+)-ATPase by nonheme iron.
The erythrocyte calmodulin-stimulated (Ca2+ + Mg2+)-ATPase (CaM-ATPase), an integral membrane protein, is inhibited in different types of congenital hemolytic anemias for which oxidative processes appear as a common feature. The oxidation of hemoglobin and its degradation lead to the accumulation of ferric heme (hemin) and nonheme iron in the red cell. We have shown previously that hemin inhibits the activity of the enzyme of normal erythrocyte (Leclerc et al. (1988) Biochim. Biophys. Acta, 946, 49-56) involving an oxidation of thiol groups. The present study demonstrates that nonheme iron also inhibits the CaM-ATPase activity. In contrast with hemin, the inhibition of the enzyme induced by the nonheme treatment is prevented by butylated hydroxytoluene, a protecting agent of unsaturated phospholipid peroxidations, while dithiothreitol, a reducing agent of protein disulfide bridges, does not restore the activity of the enzyme. We conclude that nonheme iron inhibits the enzyme at least in part, through the peroxidation of phospholipids of the membrane bilayer.
Leclerc
L
L
Institut National de la Santé et de la Recherche Médicale, Hôpital de Bicêtre, Le Kremlin-Bicêtre, France.
Marden
M
M
Poyart
C
C
D002084:Butylated Hydroxytoluene / Q000494:pharmacology; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000097:blood*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000097:blood*; D003676:Deferoxamine / Q000494:pharmacology; D004910:Erythrocyte Membrane / Q000201:enzymology*; D006418:Heme; D006801:Humans; D007501:Iron / Q000494:pharmacology*; D007700:Kinetics; D008051:Lipid Bilayers; D008563:Membrane Lipids / Q000097:blood; D010743:Phospholipids / Q000097:blood
D008051:Lipid Bilayers; D008563:Membrane Lipids; D010743:Phospholipids; D002084:Butylated Hydroxytoluene; D006418:Heme; D007501:Iron; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D003676:Deferoxamine