Cascade of caspase activation in potassium-deprived cerebellar granule neurons: Targets for treatment with peptide and protein inhibitors of apoptosis
2001 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Cascade of caspase activation in potassium-deprived cerebellar granule neurons: Targets for treatment with peptide and protein inhibitors of apoptosis
Gerhardt, E. ; Kugler, S. ; Leist, M.; Beier, C.; Berliocchi, L.; Volbracht, C. & Weller, M. et al. (2001)
Molecular and Cellular Neuroscience, 17(4) pp. 717-731. DOI: https://doi.org/10.1006/mcne.2001.0962
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- Authors
- Gerhardt, Ellen ; Kugler, S. ; Leist, Marcel; Beier, C.; Berliocchi, L.; Volbracht, C.; Weller, M; Bähr, Mathias ; Nicotera, P.; Schulz, Joerg B.
- Abstract
- 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.
- Issue Date
- 2001
- Journal
- Molecular and Cellular Neuroscience
- ISSN
- 1044-7431