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Zn2+ entry produces oxidative neuronal necrosis in cortical cell cultures.

Authors
Kim, EY; Koh, JY; Kim, YH; Sohn, S; Joe, E; Gwag, BJ
Citation
The European journal of neuroscience, 11(1):327-334, 1999
Journal Title
The European journal of neuroscience
ISSN
0953-816X1460-9568
Abstract
Evidence has accumulated that Zn2+ plays a central role in neurodegenerative processes following brain injuries including ischaemia or epilepsy. In the present study, we examined patterns and possible mechanisms of Zn2+ neurotoxicity. Inclusion of 30-300 microM Zn2+ for 30 min caused neuronal necrosis apparent by cell body and mitochondrial swelling in cortical cell cultures. This Zn2+ neurotoxicity was not attenuated by antiapoptosis agents, inhibitors of protein synthesis or caspase. Blockade of glutamate receptors or nitric oxide synthase showed no beneficial effect against Zn2+ neurotoxicity. Interestingly, antioxidants, trolox or SKF38393, attenuated Zn(2+)-induced neuronal necrosis. Pretreatment with insulin or brain-derived neurotrophic factor increased the Zn(2+)-induced free radical injury. Kainate or AMPA facilitated Zn2+ entry and potentiated Zn2+ neurotoxicity in a way sensitive to trolox. Reactive oxygen species and lipid peroxidation were generated in the early phase of Zn2+ neurotoxicity. These findings indicate that entry and accumulation of Zn2+ result in generation of toxic free radicals and then cause necrotic neuronal degeneration under certain pathological conditions in the brain.
MeSH terms
2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacologyAmino Acid Chloromethyl Ketones/pharmacologyAnimalsAntioxidants/pharmacologyApoptosis/drug effectsBrain-Derived Neurotrophic Factor/pharmacologyCells, CulturedCerebral Cortex/cytologyChromans/pharmacologyCysteine Proteinase Inhibitors/pharmacologyDizocilpine Maleate/pharmacologyDopamine Agonists/pharmacologyDrug SynergismExcitatory Amino Acid Agonists/pharmacologyExcitatory Amino Acid Antagonists/pharmacologyFemaleFree Radicals/metabolismHypoglycemic Agents/pharmacologyInsulin/pharmacologyKainic Acid/pharmacologyLipid Peroxidation/drug effectsMiceMicroscopy, ElectronMitochondrial SwellingNecrosisNerve Degeneration/chemically induced*Nerve Degeneration/metabolismNeurons/metabolism*Neurons/pathology*Neurons/ultrastructureNeurotoxins/pharmacologyOligopeptides/pharmacologyOxidative Stress/drug effectsPregnancyZinc/pharmacokinetics*Zinc/toxicity*alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/pharmacology
PMID
9987035
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Microbiology
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
AJOU Authors
손, 성향조, 은혜곽, 병주
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