DOI: 10.1073/pnas.191353598. Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity

Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity

10.1073/pnas.191353598

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Zinc is coreleased with glutamate from excitatory nerve terminals throughout the central nervous system and acutely inhibits N -methyl- d -aspartate (NMDA) receptor activation. Here we report that cultured murine cortical neurons briefly exposed to sublethal concentrations of zinc developed increased intracellular free Na + , phosphorylation of Src kinase at tyrosine 220, and tyrosine phosphorylation of NMDA receptor 2A/2B subunits, in a fashion sensitive to the Src family kinase inhibitor 4-amino-5-(4-chlorophenyl)-7-( t -butyl)pyrazolo[3,4-d]pyrimidine, PP2. Functionally, this zinc exposure produced a delayed increase in NMDA receptor current in perforated patch but not conventional whole-cell recordings, as well as an increase in NMDA receptor-mediated cell death. These observations suggest that the effect of synaptically released zinc on neuronal NMDA receptors may be biphasic: acute block, followed by Src family kinase-mediated up-regulation of NMDA receptor activity and cytotoxicity.

Bibliography

Manzerra, P., Behrens, M. M., Canzoniero, L. M. T., Wang, X. Q., Heidinger, V., Ichinose, T., Yu, S. P., & Choi, D. W. (2001). Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity. Proceedings of the National Academy of Sciences, 98(20), 11055â11061.

Authors 8

Pat Manzerra (first)
M. Margarita Behrens (additional)
Lorella M. T. Canzoniero (additional)
Xue Qing Wang (additional)
Valérie Heidinger (additional)
Tomomi Ichinose (additional)
Shan Ping Yu (additional)
Dennis W. Choi (additional)

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:34 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 5:31 a.m.)
Indexed	3 weeks, 5 days ago (Aug. 5, 2025, 9:02 a.m.)
Issued	23 years, 11 months ago (Sept. 25, 2001)
Published	23 years, 11 months ago (Sept. 25, 2001)
Published Online	23 years, 11 months ago (Sept. 25, 2001)
Published Print	23 years, 11 months ago (Sept. 25, 2001)

Funders 0

None

BibTeX

@article{Manzerra_2001, title={Zinc induces a Src family kinase-mediated up-regulation of NMDA receptor activity and excitotoxicity}, volume={98}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.191353598}, DOI={10.1073/pnas.191353598}, number={20}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Manzerra, Pat and Behrens, M. Margarita and Canzoniero, Lorella M. T. and Wang, Xue Qing and Heidinger, Valérie and Ichinose, Tomomi and Yu, Shan Ping and Choi, Dennis W.}, year={2001}, month=sep, pages={11055–11061} }

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