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Zn 2+ entry produces oxidative neuronal necrosis in cortical cell cultures
Author(s) -
Kim Eun Young,
Koh Jae Young,
Kim Yang Hee,
Sohn Seonghyang,
Joe Eunhye,
Gwag Byoung Joo
Publication year - 1999
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1999.00437.x
Subject(s) - neurotoxicity , trolox , chemistry , glutamate receptor , neuroprotection , oxidative stress , pharmacology , kainate receptor , biochemistry , ampa receptor , microbiology and biotechnology , biology , receptor , toxicity , organic chemistry , antioxidant capacity
Evidence has accumulated that Zn 2+ 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 Zn 2+ neurotoxicity. Inclusion of 30–300 μ m Zn 2+ for 30 min caused neuronal necrosis apparent by cell body and mitochondrial swelling in cortical cell cultures. This Zn 2+ 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 Zn 2+ 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 Zn 2+ entry and potentiated Zn 2+ neurotoxicity in a way sensitive to trolox. Reactive oxygen species and lipid peroxidation were generated in the early phase of Zn 2+ neurotoxicity. These findings indicate that entry and accumulation of Zn 2+ result in generation of toxic free radicals and then cause necrotic neuronal degeneration under certain pathological conditions in the brain.