INVOLVEMENT OF CASPASE-LIKE PROTEINASES IN APOPTOSIS OF NEURONAL PC12CELLS AND PRIMARY CULTURED MICROGLIA INDUCED BY 6-HYDROXYDOPAMINE

Citation
N. Takai et al., INVOLVEMENT OF CASPASE-LIKE PROTEINASES IN APOPTOSIS OF NEURONAL PC12CELLS AND PRIMARY CULTURED MICROGLIA INDUCED BY 6-HYDROXYDOPAMINE, Journal of neuroscience research, 54(2), 1998, pp. 214-222
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences
ISSN journal
0360-4012
Volume
54
Issue
2
Year of publication
1998
Pages
214 - 222
Database
ISI
SICI code
0360-4012(1998)54:2<214:IOCPIA>2.0.ZU;2-D
Abstract
Activation of proteolytic enzymes, including the caspase family of pro teinases, is a feature characteristic of the apoptotic program. In the present study, me examined a potential role of intracellular proteina ses in the death of neuronal PC12 and primary cultured rat microglial cells induced by 6-hydroxydopamine (6-OHDA), In both neuronal PC12 and microglial cells, 6-OHDA (10-200 mu M) induced apoptosis in a dose-de pendent manner as judged by the DNA break. The 6-OHDA was ineffective in Bcl-2-overexpressing neuronal PC12 cells, Pretreatment of these cel ls with two caspase inhibitors, acetyl-Try-Val-Ala-Asp-aldehyde and ac etyl-Asp-Glu-Val-Asp-aldehyde, prevented the 6-OHDA-induced apoptosis, Pepstatin A and leupeptin, potent inhibitors of aspartic and cysteine proteinases, respectively, partly inhibited the apoptosis of microgli a hut not neuronal PC12 cells, In contrast, GBR12935, a dopamine uptak e inhibitor, significantly inhibited the apoptotic death of neuronal P C12 cells but not microglia, These results suggest that mechanisms by which 6-OHDA induces apoptosis in these two cell types are distinct; 6 -OHDA incorporated into neuronal PC12 cells and its metabolites may ac tivate the caspase-like enzymes, whereas oxidative metabolites of the agent produced extracellularly may activate the caspase and the endoso mal/lysosomal proteolytic systems in microglia. J. Neurosci. Res. 54:2 14-222, 1998. (C) 1998 Wiley-Liss, Inc.