Zinc and ascorbic acid coordinately promote lipid peroxidation in brain membranes.
Zn2+ is present at high concentrations in mammalian brain, and is released in chelatable form after excitation of certain glutamatergic neurons. Recent observations suggest that it may play an important role in excitotoxic-induced neural injury. Ascorbic acid has been widely studied as a stimulator or an inhibitor of lipid-peroxide formation, depending on concentration, and lipid peroxidation has been postulated to be involved in both acute and chronic neurogenerative diseases. We find that ascorbic acid and Zn2+, at concentrations that are achieved in the brain after prolonged synaptic depolarization, coordinately promote lipid-peroxide formation and cause dysfunction of membrane-bound proteins. This effect is unique to Zn2+, and other divalent cations do not share a similar synergism with ascorbate. We propose that the Zn2+-ascorbate interaction may be an overlooked mechanism of lipid-peroxide formation in brain injury.
Diaz-Arrastia
R
R
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, USA. RDiazA@mednet.swmed.edu
Hashemi
E
E
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001205:Ascorbic Acid / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002458:Cell Fractionation; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008564:Membrane Potentials / Q000502:physiology; D018727:Muscarinic Antagonists / Q000378:metabolism / Q000494:pharmacology; D009498:Neurotoxins / Q000378:metabolism; D011813:Quinuclidinyl Benzilate / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014316:Tritium; D015032:Zinc / Q000494:pharmacology*
D000975:Antioxidants; D002614:Chelating Agents; D018727:Muscarinic Antagonists; D009498:Neurotoxins; D011976:Receptors, Muscarinic; D017392:Thiobarbituric Acid Reactive Substances; D014316:Tritium; D011813:Quinuclidinyl Benzilate; D004492:Edetic Acid; D015032:Zinc; D001205:Ascorbic Acid