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|Title:||A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury||Authors:||Chen, M.J.
Glutathione peroxidase 1
Nuclear factor (erythroid-related 2)-like 2
|Issue Date:||15-Mar-2011||Citation:||Chen, M.J., Wong, C.H.Y., Peng, Z.F., Manikandan, J., Melendez, A.J., Tan, T.M., Crack, P.J., Cheung, N.S. (2011-03-15). A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury. Free Radical Biology and Medicine 50 (6) : 736-748. ScholarBank@NUS Repository. https://doi.org/10.1016/j.freeradbiomed.2010.12.025||Abstract:||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. © 2010 Elsevier Inc. All rights reserved.||Source Title:||Free Radical Biology and Medicine||URI:||http://scholarbank.nus.edu.sg/handle/10635/109143||ISSN:||08915849||DOI:||10.1016/j.freeradbiomed.2010.12.025|
|Appears in Collections:||Staff Publications|
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