Publikation: Cascade of Caspase Activation in Potassium-Deprived Cerebellar Granule Neurons : Targets for Treatment with Peptide and Protein Inhibitors of Apoptosis
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Cerebellar granule neurons (CGN) cultured in the presence of serum and depolarizing potassium concentrations undergo apoptosis when switched to serum-free medium containing physiological potassium concentrations. Here we show that processing of the key protease, caspase-3, depends on the activation of caspase-9, but not of caspase-8. Selective peptide inhibitors of caspase-9 block processing of caspase-3 and caspase-8 and inhibit apoptosis, whereas a selective inhibitor of caspase-8 blocks neither processing of caspase-3 nor cell death. The data obtained with peptide inhibitors were confirmed by adenovirally mediated ectopic expression of the cytokine response modifier A (crmA), the baculovirus protein p35, and the X chromosome-linked inhibitor of apoptosis (XIAP). Further, caspase-8-activating death receptors do not mediate apoptosis in CGN and potassium withdrawal-induced apoptosis evolves unaltered in gld or lpr mice, which harbor mutations in the CD95/CD95 ligand system. Thus, neuronal apoptosis triggered by potassium deprivation is death receptor-independent but involves the mitochondrial pathway of caspase activation.
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GERHARDT, Ellen, Sebastian KÜGLER, Marcel LEIST, Christoph BEIER, Laura BERLIOCCHI, Christiane VOLBRACHT, Michael WELLER, Mathias BÄHR, Pierluigi NICOTERA, Jörg B. SCHULZ, 2001. Cascade of Caspase Activation in Potassium-Deprived Cerebellar Granule Neurons : Targets for Treatment with Peptide and Protein Inhibitors of Apoptosis. In: Molecular and Cellular Neuroscience. Elsevier. 2001, 17(4), pp. 717-731. ISSN 1044-7431. eISSN 1095-9327. Available under: doi: 10.1006/mcne.2001.0962BibTex
@article{Gerhardt2001-04Casca-51267, year={2001}, doi={10.1006/mcne.2001.0962}, title={Cascade of Caspase Activation in Potassium-Deprived Cerebellar Granule Neurons : Targets for Treatment with Peptide and Protein Inhibitors of Apoptosis}, number={4}, volume={17}, issn={1044-7431}, journal={Molecular and Cellular Neuroscience}, pages={717--731}, author={Gerhardt, Ellen and Kügler, Sebastian and Leist, Marcel and Beier, Christoph and Berliocchi, Laura and Volbracht, Christiane and Weller, Michael and Bähr, Mathias and Nicotera, Pierluigi and Schulz, Jörg B.} }
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