کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10958505 1100077 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Differences in the neurotoxicity profile induced by ATP and ATPγS in cultured cerebellar granule neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Differences in the neurotoxicity profile induced by ATP and ATPγS in cultured cerebellar granule neurons
چکیده انگلیسی
Extracellular ATP and P2 receptors may play a crucial role in the neurodegeneration of the CNS. Here, we investigated in neuronal cerebellar granule cultures the biological effect of the quite stable P2 receptor agonist ATPγS and compare it to the cytotoxic action of ATP. Time-course experiments showed that 500 μM ATPγS causes 50-100% cell death in 15-24 h. As proved by pharmacological means, ATPγS toxicity apparently involves neither indirect activation of NMDA receptors, nor ectonucleotidase activities, nor nucleoside transport and intracellular purine metabolism. Moreover, ATPγS induces detrimental effects without modifying the expression of several P2X and P2Y receptor proteins. Cell death instead occurs after extracellular release of the cytosolic enzyme lactic dehydrogenase and inhibition of the overall activity of the intracellular dehydrogenases. Moreover, ATPγS causes transient outflow of cytochrome c from mitochondria (maximal 2.5-fold stimulation in 4 h), it raises the intracellular reactive oxygen species (about four-fold in 1 h) and cAMP levels (about 40% in 15 min-4 h). Among several P2 receptor antagonists, only pyridoxal-phosphate-6-azophenyl-2′,4′-disulphonic acid 4-sodium promotes 80-100% neuroprotection.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 47, Issue 5, October 2005, Pages 334-342
نویسندگان
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