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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.
Wong, C.H.Y.
Peng, Z.F.
Manikandan, J.
Melendez, A.J.
Tan, T.M. 
Crack, P.J.
Cheung, N.S.
Keywords: Free radicals
Glutathione peroxidase 1
Ischemic stroke
Nuclear factor (erythroid-related 2)-like 2
Ubiquitinproteasome pathway
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.
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
ISSN: 08915849
DOI: 10.1016/j.freeradbiomed.2010.12.025
Appears in Collections:Staff Publications

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