Iron-catalyzed lipid peroxidation in aortic cells in vitro: protective effect of extracellular magnesium.
Low serum Mg2+ has been associated with an increased incidence of cardiovascular pathology in human populations. We investigated the effect of extracellular Mg2+ on Fe-catalyzed lipid peroxidation in rat aortic segments and in human aortic smooth muscle cells. Products of phospholipid oxidation [malonaldehyde (MDA) and 4-hydroxyalkenals (4-HA)], loss of fatty acyl double bonds (by proton-NMR) and glutathione levels indicated that exogenous ferric ions were several-fold more effective than ferrous ions in causing lipid peroxidation. Increased peroxidation was detectable at <1.0 microM Fe3+. Exogenous ferric iron-ionophore, 8-hydroxyquinoline, did not increase peroxidation by ferric ion, suggesting that Fe-catalyzed lipid peroxidation occurred at the cell surface. As ionized serum [Mg2+](o) was lowered from the physiological (0.7-0.96 mM) into the pathophysiological range (0.3-0.5mM) in Fe3+-containing medium, MDA/4-HA levels increased two to three-fold, with a concomitant loss of fatty acyl double bonds and decreased extracellular glutathione. Conversely, MDA/4-HA decreased as ionized Mg2+ was increased, accompanied by a rise in extracellular glutathione. The results indicate that Mg2+ protects aortic cell plasma membranes from ferric iron-catalyzed lipid peroxidation and that this is a contributing factor in the protective action of ionized Mg2+ on the cardiovascular system.
Kostellow
Adele B
AB
Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Morrill
Gene A
GA
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005290:Ferric Compounds / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008274:Magnesium / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D015125:Oxyquinoline / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000447:Aldehydes; D005290:Ferric Compounds; D005296:Ferrous Compounds; D007476:Ionophores; D008315:Malondialdehyde; D015125:Oxyquinoline; D007501:Iron; D005978:Glutathione; D008274:Magnesium