TY - JOUR
T1 - A global transcriptomic view of the multifaceted role of glutathione peroxidase-1 in cerebral ischemic-reperfusion injury
AU - Chen, Minghui Jessica
AU - Wong, Connie Hoi Yee
AU - Peng, Zhao Feng
AU - Manikandan, Jayapal
AU - Melendez, Alirio J
AU - Tan, Theresa M
AU - Crack, Peter John
AU - Sang Cheung, Nam
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21193029
U2 - 10.1016/j.freeradbiomed.2010.12.025
DO - 10.1016/j.freeradbiomed.2010.12.025
M3 - Article
SN - 0891-5849
VL - 50
SP - 736
EP - 748
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 6
ER -