کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998404 | 1115627 | 2005 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
β-Carbolines induce apoptosis in cultured cerebellar granule neurons via the mitochondrial pathway
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
OMMPTPΔΨmβCCGNCyAVDACMTT - MTTβ-carboline - β-کاربولینβ-Carbolines - β-کاربولین هاAIF - آیفونBongkrekic acid - اسید بونکروکیکPermeability transition pore - افت فشار نفوذ پذیریimm - انحصارApoptosis - خزان یاختهایinner mitochondrial membrane - درونی غشای میتوکندریcyclosporin A - سیکلوسپورین Aapoptosis-inducing factor - عامل القاء آپوپتوزouter mitochondrial membrane - غشای بیرونی میتوکندریMitochondrion - میتوکندریونcerebellar granule neuron - نورون گرانول مخچهcerebellar granule neurons - نورونهای گرانشی مخچهMitochondrial membrane potential - پتانسیل غشای میتوکندریCaspases - کاسپازvoltage-dependent anion channel - کانال آنیون وابسته به ولتاژ
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 48, Issue 1, January 2005, Pages 105-117
Journal: Neuropharmacology - Volume 48, Issue 1, January 2005, Pages 105-117
نویسندگان
Grégory Hans, Brigitte Malgrange, François Lallemend, Jessica Crommen, Sabine Wislet-Gendebien, Shibeshih Belachew, Pierre Robe, Bernard Rogister, Gustave Moonen, Jean-Michel Rigo,