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Iron-catalyzed lipid peroxidation in aortic cells in vitro: protective effect of extracellular magnesium
Adele B Kostellow1, Gene A Morrill
1Department of Physiology and Biophysics, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Abstract:
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.
Insights
Low extracellular magnesium (Mg2+) levels exacerbate iron-catalyzed lipid peroxidation in aortic cells. Increasing Mg2+ protects against this process, highlighting its role in cardiovascular health.
Area of Science:
- Biochemistry
- Cardiovascular Biology
- Cellular Physiology
Background:
- Low serum magnesium (Mg2+) is linked to increased cardiovascular disease incidence.
- Iron-catalyzed lipid peroxidation is a key process in cardiovascular pathology.
Purpose of the Study:
- To investigate the impact of extracellular Mg2+ on iron-catalyzed lipid peroxidation in aortic tissues and cells.
- To elucidate the protective mechanisms of Mg2+ against cardiovascular damage.
Main Methods:
- Experiments conducted on rat aortic segments and human aortic smooth muscle cells.
- Assessed lipid peroxidation products (malonaldehyde, 4-hydroxyalkenals) and glutathione levels.
- Utilized proton-NMR to evaluate fatty acyl double bond integrity.
Main Results:
- Ferric iron (Fe3+) was more potent than ferrous iron (Fe2+) in inducing lipid peroxidation.
- Reduced extracellular Mg2+ significantly increased lipid peroxidation and decreased glutathione levels.
- Increased extracellular Mg2+ inhibited lipid peroxidation and elevated glutathione levels.
Conclusions:
- Extracellular Mg2+ protects aortic cell plasma membranes from Fe3+-catalyzed lipid peroxidation.
- Mg2+ plays a crucial role in the cardiovascular protective effects of ionized magnesium.
