کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10958522 1100080 2005 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Purine nucleoside-mediated protection of chemical hypoxia-induced neuronal injuries involves p42/44 MAPK activation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Purine nucleoside-mediated protection of chemical hypoxia-induced neuronal injuries involves p42/44 MAPK activation
چکیده انگلیسی
Hypoxia in brain may lead to cell death by apoptosis and necrosis. Concomitant is the formation of purine nucleosides, e.g. adenosine, a powerful endogenous neuroprotectant. Despite vigorous studies, many aspects of the mechanisms involved in purine-based protection are still unclear. In this study, we wanted to investigate the effect of purine nucleosides on cellular responses to chemical hypoxia. O2-sensitive neuronal pheochromocytoma (PC12)-cells, which are widely used as a model system for sympathetic ganglion-like neurons, were subjected to chemical hypoxia induced with rotenone, an inhibitor of mitochondrial complex I. Adenosine and its relatives guanosine and inosine were tested for their neuroprotective capability to improve neurite outgrowth and viability. In addition, cell lysates were analyzed for mitogen-activated-protein-kinases (MAPK) activation by anti-active and anti-total MAPKinase immunoblotting. Adenosine, guanosine and inosine significantly inhibited the loss of viability after hypoxic insult. In combination with NGF, purine nucleosides also partially rescued neurite outgrowth. The MEK-1/-2 inhibitor PD098059 inhibited purine nucleoside-mediated protection up to 85.23% and also markedly decreased neurite formation induced by NGF and purine nucleosides in hypoxic cells. Immunoblot analysis revealed a strong activation of MAPKinase upon incubation of cells with adenosine, guanosine or inosine. In combination with NGF an additive effect was observed. Results suggested that activation of the MAPKinase pathway plays a vital role in purine nucleoside-mediated protection of neuronal cells following hypoxic insult.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurochemistry International - Volume 46, Issue 7, June 2005, Pages 513-521
نویسندگان
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