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A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury

Citation

Chen, MJ and Wong, CHY and Peng, ZF and Manikandan, J and Melendez, AJ and Tan, TM and Crack, PJ and Cheung, NS, A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury, Free Radical Biology and Medicine, 50, (6) pp. 736-748. ISSN 0891-5849 (2011) [Refereed Article]


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DOI: doi: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 24h 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.

Item Details

Item Type:Refereed Article
Keywords:Glutathione peroxidase 1; Ischemic stroke; Microarray; Ubiquitin-proteasome pathway; Nuclear factor (erythroid-related 2)-like 2; Neurodegeneration; Free radicals
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Chen, MJ (Ms Minghui Chen)
Author:Cheung, NS (Dr Nam Cheung)
ID Code:69813
Year Published:2011
Web of Science® Times Cited:12
Deposited By:Menzies Institute for Medical Research
Deposited On:2011-05-19
Last Modified:2017-11-17
Downloads:0

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