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The effect of magnesium on oxidative neuronal injury in vitro
1Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Abstract:
The effect of magnesium on the oxidative neuronal injury induced by hemoglobin was assessed in murine cortical cell cultures. Exposure to 5 microM hemoglobin in physiologic (1 mM) magnesium for 26 h resulted in the death of about one-half the neurons and a sixfold increase in malondialdehyde production; glia were not injured. Increasing medium magnesium to 3 mM reduced neuronal death by about one-half and malondialdehyde production by about two-thirds; neuronal death and lipid peroxidation were approximately doubled in 0.3 mM magnesium. Comparable results were observed in spinal cord cultures. The NMDA antagonist MK-801 weakly attenuated hemoglobin neurotoxicity in low-magnesium medium, but tended to potentiate injury in physiologic magnesium. Incubation in low-magnesium medium alone for 24 h reduced cellular glutathione by approximately 50% in mixed neuronal and glial cultures but by only 10% in pure glial cultures. The iron-dependent oxidation of phosphatidylethanolamine liposomes was attenuated in a concentration-dependent fashion by 2.5-10 mM magnesium; a similar effect was provided by 0.01-0.1 mM cobalt. However, oxidation was weakly enhanced by 0.5-1 mM magnesium. These results suggest that the vulnerability of neurons to iron-dependent oxidative injury is an inverse function of the extracellular magnesium concentration. At high concentrations, magnesium inhibits lipid peroxidation directly, perhaps by competing with iron for phospholipid binding sites. At low concentrations, enhancement of cell death may be due to the combined effect of increased NMDA receptor activity, glutathione depletion, and direct potentiation of lipid peroxidation.
Insights
Magnesium protects neurons from hemoglobin-induced oxidative injury. Higher magnesium levels reduce neuronal death and lipid peroxidation, while lower levels increase vulnerability by affecting NMDA receptors and glutathione.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Hemoglobin can induce oxidative stress and neuronal injury.
- Extracellular magnesium ions play a role in neuronal function and protection.
- The precise mechanisms by which magnesium influences hemoglobin-induced neurotoxicity are not fully understood.
Purpose of the Study:
- To investigate the effect of extracellular magnesium concentration on hemoglobin-induced oxidative neuronal injury.
- To elucidate the role of magnesium in modulating lipid peroxidation and neuronal cell death.
Main Methods:
- Murine cortical and spinal cord cell cultures were exposed to hemoglobin under varying magnesium concentrations.
- Lipid peroxidation was assessed by measuring malondialdehyde production.
- Glutathione levels and NMDA receptor antagonist effects were also evaluated.
Main Results:
- Increased magnesium concentrations (3 mM) significantly reduced neuronal death and malondialdehyde production induced by hemoglobin.
- Low magnesium concentrations (0.3 mM) exacerbated neuronal injury and lipid peroxidation.
- Magnesium inhibited iron-dependent oxidation of liposomes in a concentration-dependent manner at higher concentrations, but enhanced it at lower concentrations.
Conclusions:
- Neuronal vulnerability to oxidative injury is inversely related to extracellular magnesium concentration.
- Magnesium exerts neuroprotection by directly inhibiting lipid peroxidation and potentially through other mechanisms at physiological concentrations.
- Low magnesium levels may potentiate neurotoxicity via increased NMDA receptor activity, glutathione depletion, and enhanced lipid peroxidation.
