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Glutamate mobilizes [Zn 2+ ] i through Ca 2+ ‐dependent reactive oxygen species accumulation
Author(s) -
Dineley Kirk E.,
Devinney II Michael J.,
Zeak Jennifer A.,
Rintoul Gordon L.,
Reynolds Ian J.
Publication year - 2008
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2008.05536.x
Subject(s) - glutamate receptor , nmda receptor , biophysics , chemistry , metabotropic glutamate receptor , reactive oxygen species , endogeny , zinc , intracellular , cytosol , glutamic acid , mitochondrion , biochemistry , nitric oxide , receptor , biology , amino acid , enzyme , organic chemistry
Liberation of zinc from intracellular stores contributes to oxidant‐induced neuronal injury. However, little is known regarding how endogenous oxidant systems regulate intracellular free zinc ([Zn 2+ ] i ). Here we simultaneously imaged [Ca 2+ ] i and [Zn 2+ ] i to study acute [Zn 2+ ] i changes in cultured rat forebrain neurons after glutamate receptor activation. Neurons were loaded with fura‐2FF and FluoZin‐3 to follow [Ca 2+ ] i and [Zn 2+ ] i , respectively. Neurons treated with glutamate (100 μM) for 10 min gave large Ca 2+ responses that did not recover after termination of the glutamate stimulus. Glutamate also increased [Zn 2+ ] i , however glutamate‐induced [Zn 2+ ] i changes were completely dependent on Ca 2+ entry, appeared to arise entirely from internal stores, and were substantially reduced by co‐application of the membrane‐permeant chelator TPEN during the glutamate treatment. Pharmacological maneuvers revealed that a number of endogenous oxidant producing systems, including nitric oxide synthase, phospholipase A 2 , and mitochondria all contributed to glutamate‐induced [Zn 2+ ] i changes. We found no evidence that mitochondria buffered [Zn 2+ ] i during acute glutamate receptor activation. We conclude that glutamate‐induced [Zn 2+ ] i transients are caused in part by [Ca 2+ ] i ‐induced reactive oxygen species that arises from both cytosolic and mitochondrial sources.