Elsevier

Neuroscience Letters

Volume 352, Issue 2, 4 December 2003, Pages 105-108
Neuroscience Letters

Down-regulation of GluR2 is associated with Ca2+-dependent protease activities in kainate-induced apoptotic cell death in culturd rat hippocampal neurons

https://doi.org/10.1016/j.neulet.2003.08.054Get rights and content

Abstract

In the present study, the molecular mechanisms underlying kainate-induced neurotoxicity were characterized in cultured rat hippocampal neurons. Long-term exposure to kainate caused typically apoptotic cell death, which was accompanied by the accumulation of calcium, marked down-regulation of GluR2 subunit, and the activation of calpain and caspase-3. All these alterations were prevented by alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist CNQX, but not by NMDA receptor antagonist MK801 and membrane L-type calcium channel antagonist nifedipine. In the presence of cyclothiazide, kainate-induced neurotoxicity was significantly enhanced. Inhibition of either caspases by zVAD-fmk or calpains by calpeptin protected neurons from neurotoxicity. These results suggest that long-term exposure of hippocampal neurons to kainate causes apoptosis, whose mechanisms involve multiple Ca2+-dependent cascades, in which AMPA receptor subunits may be targets for Ca2+-activated protease-mediated degradation during kainate-induced neuron apoptosis.

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Acknowledgements

We thank Dr P. Worley (Johns Hopkins University School of Medicine) for providing anti-GluR1 and -GluR2 antibodies. This study was supported in part by grants from the National Natural Science Foundation of China (30271448) and the Ministry of Education Foundation of China (2003).

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