Reference : beta-carbolines induce apoptosis in cultured cerebellar granule neurons via the mitoc...
Scientific journals : Article
Social & behavioral sciences, psychology : Neurosciences & behavior
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/4841
beta-carbolines induce apoptosis in cultured cerebellar granule neurons via the mitochondrial pathway
English
Hans, Grégory mailto [Centre Hospitalier Universitaire de Liège - CHU > > Anesthésie et réanimation >]
Malgrange, Brigitte mailto [Université de Liège - ULg > > CNCM/ Centre fac. de rech. en neurobiologie cell. et moléc. >]
Lallemend, François [> > > >]
Crommen, Jacques mailto [Université de Liège - ULg > Département de pharmacie > Analyse des médicaments >]
Wislet-Gendebien, Sabine mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Belachew, Shibeshih mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie >]
Robe, Pierre mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Génétique générale et humaine >]
Rogister, Bernard mailto [Université de Liège - ULg > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine >]
Moonen, Gustave mailto [Université de Liège - ULg > Département des sciences cliniques > Neurologie - Doyen de la Faculté de Médecine]
Rigo, Jean-Michel [Universiteit Hasselt - UH > > > >]
Jan-2005
Neuropharmacology
Pergamon-Elsevier Science Ltd
48
1
105-117
Yes (verified by ORBi)
International
0028-3908
Oxford
[en] apoptosis ; mitochondrion ; caspases ; beta-carbolines ; cerebellar granule neurons
[en] N-Butyl-beta-carboline-3-carboxylate (betaCCB) is, together with 2-methyl-norharmanium and 2,9-dimethylnorharmanium ions, an endogenously occurring beta-carboline. Due to their structural similarities with the synthetic neurotoxin 1-methy14-phenyl-1,2,3,6-tetrahydropyridine (MPTP), harman and norharman compounds have been proposed to be involved in the pathogenesis of Parkinson's disease. While also structurally related, betaCCB has received much less interest in that respect although we had previously demonstrated that it induces the apoptotic cell death of cultured cerebellar granule neurons (CGNs). Herein, we have investigated the molecular events leading to CGN apoptosis upon betaCCB treatment. We first demonstrated that betaCCB-induced apoptosis occurs in neurons only, most likely as a consequence of a specific neuronal uptake as shown using binding/uptake experiments. Then we observed that, in betaCCB-treated CGNs, caspases 9, 3 and 8 were successively activated, suegesing an activation of the mitochondrial pathway. Consistently, betaCCB also induced the release from the mitochondrial intermembrane space of two pro-apoptotic factors. i.e. cytochrome c and apotptosis inducing factor (AIF). Interestingly, no mitochondrial membrane depolarisation was associated with this release. suggesting a mitochondrial permeability transition pore-independent mechanism. The absence of any neuroprotective effect provided by two mPTP inhibitors. i.e. cyclosporine A and bongkrekic acid. further supported this hypothesis. Together. these results show that betaCCB is specifically taken up by neuronal cells where it triggers a specific permeabilization of the outer mitochondrial membrane and a subsequent apoptotic cell death. (C) 2004 Elsevier Ltd. All rights reserved.
Fonds de la Recherche Scientifique (Communauté française de Belgique) - F.R.S.-FNRS
Researchers ; Professionals
http://hdl.handle.net/2268/4841
10.1016/j.neuropharm.2004.09.001

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
Neuropharmacology (2005) - hans.pdfNo commentaryPublisher postprint613.31 kBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.