DOI: 10.1073/pnas.94.21.11657. Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons

Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons

10.1073/pnas.94.21.11657

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Neurotoxicity induced by overstimulation of N -methyl- d -aspartate (NMDA) receptors is due, in part, to a sustained rise in intracellular Ca 2+ ; however, little is known about the ensuing intracellular events that ultimately result in cell death. Here we show that overstimulation of NMDA receptors by relatively low concentrations of glutamate induces apoptosis of cultured cerebellar granule neurons (CGNs) and that CGNs do not require new RNA or protein synthesis. Glutamate-induced apoptosis of CGNs is, however, associated with a concentration- and time-dependent activation of the interleukin 1β-converting enzyme (ICE)/CED-3-related protease, CPP32/Yama/apopain (now designated caspase 3). Further, the time course of caspase 3 activation after glutamate exposure of CGNs parallels the development of apoptosis. Moreover, glutamate-induced apoptosis of CGNs is almost completely blocked by the selective cell permeable tetrapeptide inhibitor of caspase 3, Ac-DEVD-CHO but not by the ICE (caspase 1) inhibitor, Ac-YVAD-CHO. Western blots of cytosolic extracts from glutamate-exposed CGNs reveal both cleavage of the caspase 3 substrate, poly(ADP-ribose) polymerase, as well as proteolytic processing of pro-caspase 3 to active subunits. Our data demonstrate that glutamate-induced apoptosis of CGNs is mediated by a posttranslational activation of the ICE/CED-3-related cysteine protease caspase 3.

Bibliography

Du, Y., Bales, K. R., Dodel, R. C., Hamilton-Byrd, E., Horn, J. W., Czilli, D. L., Simmons, L. K., Ni, B., & Paul, S. M. (1997). Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granuleâneurons. Proceedings of the National Academy of Sciences, 94(21), 11657â11662.

Authors 9

Yansheng Du (first)
Kelly R. Bales (additional)
Richard C. Dodel (additional)
Elizabeth Hamilton-Byrd (additional)
Jeffrey W. Horn (additional)
Dan L. Czilli (additional)
Linda K. Simmons (additional)
Binhui Ni (additional)
Steven M. Paul (additional)

References 45 Referenced 235

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:42 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 2:27 p.m.)
Indexed	1 week, 2 days ago (Aug. 21, 2025, 12:58 p.m.)
Issued	27 years, 10 months ago (Oct. 14, 1997)
Published	27 years, 10 months ago (Oct. 14, 1997)
Published Online	27 years, 10 months ago (Oct. 14, 1997)
Published Print	27 years, 10 months ago (Oct. 14, 1997)

Funders 0

None

BibTeX

@article{Du_1997, title={Activation of a caspase 3-related cysteine protease is required for glutamate-mediated apoptosis of cultured cerebellar granule neurons}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.21.11657}, DOI={10.1073/pnas.94.21.11657}, number={21}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Du, Yansheng and Bales, Kelly R. and Dodel, Richard C. and Hamilton-Byrd, Elizabeth and Horn, Jeffrey W. and Czilli, Dan L. and Simmons, Linda K. and Ni, Binhui and Paul, Steven M.}, year={1997}, month=oct, pages={11657–11662} }

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}