کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
9415741 1614324 2005 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Nitric oxide applications prior and simultaneous to potentially excitotoxic NMDA-evoked calcium transients: Cell death or survival
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
Nitric oxide applications prior and simultaneous to potentially excitotoxic NMDA-evoked calcium transients: Cell death or survival
چکیده انگلیسی
Nitric oxide (NO) is a molecule that plays a prominent role in neurotoxic as well as neuroprotective pathways. Here, we investigated the effects of NO on potentially excitotoxic glutamate-induced intracellular calcium ([Ca2+]i) dynamics. Our hypothesis was that pre- and coexposure to NO in conjunction with glutamate receptor stimulation modulates [Ca2+]i responses differentially. [Ca2+]i transients, assessed by the fluorescent cytosolic Ca2+ indicator dye fluo-4, were elicited in mouse striatal neurons by consecutive NMDA applications (200 μM for 100 s each). Subgroups of neuronal cultures were additionally exposed to a NO donor (S-nitroso-N-acetyl-d,l-penicillamine, SNAP, 50-500 μM), either by pre- (for 6 h prior to NMDA) or cotreatment (for 30 min during NMDA). Pretreatment with NO led to dramatically decreased NMDA-evoked [Ca2+]i rises in comparison to controls (NMDA alone). Annexin V/propidium iodide staining showed consistently that NO pretreatment is protective against NMDA-induced cell death. In contrast, NO/NMDA cotreatment caused a potentiation of [Ca2+]i rises, whereby the duration of [Ca2+]i transients following NMDA application was prolonged and remained at an increased plateau level. Simultaneous application of the mitochondrial permeability transition pore (mtPTP) blocker cyclosporin A (2 μM) during the NO/NMDA cotreatment prevented the deregulation of [Ca2+]i. The observed [Ca2+]i deregulation was accompanied by a decrease in the mitochondrial membrane potential as indicated by tetramethylrhodamine methylester (TMRM) fluorescence. These findings suggest that NO can act in a protective way due to preconditioning or can have a possibly detrimental impact in case of acute release. They provide a possible explanation for the ambivalence of NO in neurodegenerative processes where glutamate receptor stimulation and mitochondrial [Ca2+]i sequestration are causally involved.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1060, Issues 1–2, 26 October 2005, Pages 1-15
نویسندگان
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