Neural precursor cells (NPCs) critically regulate brain morphogenesis and recent studies have revealed an unexpectedly high frequency of NPC chromosomal abnormalities and apoptosis in the developing brain. We have shown previously that the apoptotic response of NPCs to genotoxic agents is dependent on p53 and caspase-9, but not Bax or caspase-3 expression. In this study, we found that NPCs deficient in Apaf-1, or both the pro-apoptotic multidomain Bcl-2 family members Bax and Bak, were resistant to cytosine arabinoside and Î³-irradiation-induced apoptosis. Inhibitors of gene transcription, protein translation, and caspase activity also blocked genotoxin-induced NPC apoptosis. Although caspase-3 and caspase-6 were both cleaved in response to DNA damage, neither of these effector caspases was critical for apoptosis. Genotoxin-induced NPC death was accompanied by the generation of reactive oxygen species and could be inhibited by several known antioxidants. Conversely, DNA damage-induced reactive oxygen species generation was inhibited significantly by gene disruption of p53, Apaf-1, or caspase-9, and combined deficiency of Bax and Bak, but not by caspase-3 or caspase-6 deficiency. These studies suggest that caspase-9 activation is both necessary and sufficient for genotoxin-induced neural precursor cell reactive oxygen species generation and death. Â© 2003 Wiley-Liss, Inc.
D'Sa, C., Klocke, B.J., Cecconi, F., Lindsten, T., Thompson, C.B., Korsmeyer, S., et al. (2003). Caspase Regulation of Genotoxin-Induced Neural Precursor Cell Death. JOURNAL OF NEUROSCIENCE RESEARCH, 74(3), 435-445.
|Tipologia:||Articolo su rivista|
|Citazione:||D'Sa, C., Klocke, B.J., Cecconi, F., Lindsten, T., Thompson, C.B., Korsmeyer, S., et al. (2003). Caspase Regulation of Genotoxin-Induced Neural Precursor Cell Death. JOURNAL OF NEUROSCIENCE RESEARCH, 74(3), 435-445.|
|IF:||Con Impact Factor ISI|
|Settore Scientifico Disciplinare:||Settore BIO/06|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1002/jnr.10738|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2003|
|Titolo:||Caspase Regulation of Genotoxin-Induced Neural Precursor Cell Death|
|Autori:||D'Sa, C; Klocke, BJ; Cecconi, F; Lindsten, T; Thompson, CB; Korsmeyer, S; Flavell, RA; Roth, KA|
|Appare nelle tipologie:||01 - Articolo su rivista|