Glutamate mobilizes [Zn2+] through Ca2+ -dependent reactive oxygen species accumulation.

Journal Article (Journal Article)

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 microM) 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.

Full Text

Duke Authors

Cited Authors

  • Dineley, KE; Devinney, MJ; Zeak, JA; Rintoul, GL; Reynolds, IJ

Published Date

  • September 2008

Published In

Volume / Issue

  • 106 / 5

Start / End Page

  • 2184 - 2193

PubMed ID

  • 18624907

Pubmed Central ID

  • PMC3815702

Electronic International Standard Serial Number (EISSN)

  • 1471-4159

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2008.05536.x


  • eng

Conference Location

  • England