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• W2034303889 abstract "N-Butyl-β-carboline-3-carboxylate (βCCB) is, together with 2-methyl-norharmanium and 2,9-dimethylnorharmanium ions, an endogenously occurring β-carboline. Due to their structural similarities with the synthetic neurotoxin 1-methyl-4-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, βCCB 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 βCCB treatment. We first demonstrated that βCCB-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 βCCB-treated CGNs, caspases 9, 3 and 8 were successively activated, suggesting an activation of the mitochondrial pathway. Consistently, βCCB 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 βCCB is specifically taken up by neuronal cells where it triggers a specific permeabilization of the outer mitochondrial membrane and a subsequent apoptotic cell death." @default.
• W2034303889 created "2016-06-24" @default.
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• W2034303889 date "1988-01-01" @default.
• W2034303889 modified "2023-10-06" @default.
• W2034303889 title "Determination of n-butyl-β-carboline-3-carboxylate in aqueous brain extracts" @default.
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• W2034303889 doi "https://doi.org/10.1016/s0378-4347(00)83084-4" @default.
• W2034303889 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/3235530" @default.
• W2034303889 hasPublicationYear "1988" @default.
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