کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909230 1046713 2011 13 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic–reperfusion injury
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic–reperfusion injury
چکیده انگلیسی

Transient cerebral ischemia often results in secondary ischemic/reperfusion injury, the pathogenesis of which remains unclear. This study provides a comprehensive, temporal description of the molecular events contributing to neuronal injury after transient cerebral ischemia. Intraluminal middle cerebral artery occlusion (MCAO) was performed to induce a 2-h ischemia with reperfusion. Microarray analysis was then performed on the infarct cortex of wild-type (WT) and glutathione peroxidase-1 (a major antioxidant enzyme) knockout (Gpx1−/−) mice at 8 and 24 h postreperfusion to identify differential gene expression profile patterns and potential alternative injury cascades in the absence of Gpx1, a crucial antioxidant enzyme, in cerebral ischemia. Genes with at least ± 1.5-fold change in expression at either time point were considered significant. Global transcriptomic analyses demonstrated that 70% of the WT-MCAO profile overlapped with that of Gpx1−/−-MCAO, and 28% vice versa. Critical analysis of the 1034 gene probes specific to the Gpx1−/−-MCAO profile revealed regulation of additional novel pathways, including the p53-mediated proapoptotic pathway and Fas ligand (CD95/Apo1)-mediated pathways; downplay of the Nrf2 antioxidative cascade; and ubiquitin–proteasome system dysfunction. Therefore, this comparative study forms the foundation for the establishment of screening platforms for target definition in acute cerebral ischemia intervention.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 50, Issue 6, 15 March 2011, Pages 736–748
نویسندگان
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