Prevention of apoptotic neuronal death by controlling procaspases? A point of view

Dubois-Dauphin, Michel; Pfister, Yvan; Vallet, Philippe; Savioz, Armand

doi:10.1016/s0165-0173(01)00095-9

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Title		Prevention of apoptotic neuronal death by controlling procaspases? A point of view
Authors		Dubois-Dauphin, Michel Pfister, Yvan Vallet, Philippe Savioz, Armand
Published in		Brain Research Reviews. 2001, vol. 36, no. 2-3, p. 196-203
Abstract		In various animal models of neurodegenerative diseases the long-lasting control of cell death by anti-apoptotic therapies is not successful. We present here our view on the control of procaspase expression in a model of cerebral stroke. We have investigated how Hu-Bcl-2 overexpression modifies cell death protein activation in a model of cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO). In wild type mice MCAO induced release of cytochrome c from the mitochondria, and activation of caspases 9 and 3. In parallel with caspases activation, procaspase 9 and procaspase 3 were, respectively, increased and decreased. In Hu-Bcl-2 transgenic mice cytochrome c release and caspases 9 and 3 activation were blocked. However procaspase 9 increased, like in wt mice, but procaspase 3 remained unchanged. By 2 weeks after MCAO caspases were no longer blocked in Hu-Bcl-2 transgenic mice. Procaspase 9 increase could represent a time bomb in Hu-Bcl-2 mice where caspase 9 activation is blocked. Indeed, cellular accumulation of procaspase 9 is a potentially harmful event able to overcome anti-apoptotic protection by Bcl-2 and threaten cells with rapid destruction. Through understanding of the upstream regulation of procaspase 9, early targets for the pharmacological control of apoptotic cell death may be revealed.
Keywords		Animals — Apoptosis/physiology — Brain Ischemia/drug therapy/enzymology/physiopathology — Caspase 9 — Caspases/metabolism — Enzyme Precursors/metabolism — Gene Expression Regulation, Enzymologic/physiology — Humans — Mice — Mice, Transgenic — Neurodegenerative Diseases/drug therapy/enzymology/physiopathology — Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
Identifiers		DOI: 10.1016/s0165-0173(01)00095-9 PMID: 11690616
Full text		Article (Published version) (338 Kb) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie Faculté des sciences / Section de biologie / Département de génétique et évolution
Citation (ISO format)		DUBOIS-DAUPHIN, Michel et al. Prevention of apoptotic neuronal death by controlling procaspases? A point of view. In: Brain Research Reviews, 2001, vol. 36, n° 2-3, p. 196-203. doi: 10.1016/s0165-0173(01)00095-9 https://archive-ouverte.unige.ch/unige:26602