Genome-wide gene expression analysis for induced ischemic tolerance and delayed neuronal death following transient global ischemia in rats.
Genome-wide gene expression analysis of the hippocampal CA1 region was conducted in a rat global ischemia model for delayed neuronal death and induced ischemic tolerance using an oligonucleotide-based DNA microarray containing 8,799 probes. The results showed that expression levels of 246 transcripts were increased and 213 were decreased following ischemia, corresponding to 5.1% of the represented probe sets. These changes were divided into seven expression clusters using hierarchical cluster analysis, each with distinct conditions and time-specific patterns. Ischemic tolerance was associated with transient up-regulation of transcription factors (c-Fos, JunB Egr-1, -2, -4, NGFI-B), Hsp70 and MAP kinase cascade-related genes (MKP-1), which are implicated cell survival. Delayed neuronal death exhibited complex long-lasting changes of expression, such as up-regulation of proapoptotic genes (GADD153, Smad2, Dral, Caspase-2 and -3) and down-regulation of genes implicated in survival signaling (MKK2, and PI4 kinase, DAG/PKC signaling pathways), suggesting an imbalance between death and survival signals. Our study provides a differential gene expression profile between delayed neuronal death and induced ischemic tolerance in a genome-wide analysis, and contributes to further understanding of the complex molecular pathophysiology in cerebral ischemia.
Kawahara
Nobutaka
N
Department of Neurosurgery, Faculty of Medicine, University of Tokyo, Japan. kawahara-tky@umin.ac.jp
Wang
Yan
Y
Mukasa
Akitake
A
Furuya
Kazuhide
K
Shimizu
Tatsuya
T
Hamakubo
Takao
T
Aburatani
Hiroyuki
H
Kodama
Tatsuhiko
T
Kirino
Takaaki
T
D000818:Animals; D002545:Brain Ischemia / Q000503:physiopathology*; D016923:Cell Death; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016678:Genome; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D012333:RNA, Messenger