The effect of magnesium on oxidative neuronal injury in vitro.
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.
Regan
R F
RF
Division of Emergency Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Jasper
E
E
Guo
Y
Y
Panter
S S
SS
D000818:Animals; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice / Q000196:embryology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009498:Neurotoxins / Q000494:pharmacology; D018384:Oxidative Stress / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D006454:Hemoglobins; D018696:Neuroprotective Agents; D009498:Neurotoxins; D008315:Malondialdehyde; D016291:Dizocilpine Maleate; D005978:Glutathione; D008274:Magnesium