Neuroprotective gene expression profiles in ischemic cortical cultures preconditioned with IGF-1 or bFGF.
The mechanisms underlying growth factor preconditioning of neurons are only partially elucidated, and no studies have been conducted in this area using a gene profiling approach. We used cDNA microarrays to compare the transcriptional profiles of cells preconditioned either with insulin-like growth factor I (IGF-1) or basic fibroblast growth factor (bFGF), to identify differentially regulated genes that may function in growth factor signaling, response to oxygen-glucose deprivation (OGD), and most importantly, cell survival. Primary rat cortical cultures were treated with bFGF or IGF-1 for 2, 24, or 24 h followed by OGD for 90 min, and compared with cells that were subject to OGD without growth factor pretreatment. Although the majority of surveyed genes were unchanged in all experimental treatments, 175 genes (10% of the cDNAs on the chip) were found to be differentially regulated in at least one of the treatment conditions. Hierarchical clustering of these 175 genes was used to identify four expression clusters: IGF-1 regulated, bFGF regulated, OGD regulated, and putative neuroprotective genes. Further analysis using realtime RT-PCR confirmed that we had identified genes that are regulated by single growth factors, as well as several more that are co-regulated by both IGF-1 and bFGF. These genes can influence neuronal survival by affecting diverse pathways such as growth factor signal transduction (CD44, DTR, DUSP6, EPS8, IGFBP3), DNA repair and transcription (FOXJ1), metabolic homeostasis (RASA1, SHMT2), cytoskeletal stability (MSN, MAPT) and cholesterol biosynthesis (FDFT1, FDPS).
Yoshida
Erin
E
Molecular Signaling Group, Institute for Biological Sciences, National Research Council Canada, M-54, 1200 Montreal Rd., Ottawa, Ontario, K1A 0R6, Canada. Erin.Yoshida@nrc-cnrc.gc.ca
Atkinson
Trevor G
TG
Chakravarthy
Balu
B
D000818:Animals; D002545:Brain Ischemia / Q000235:genetics* / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D020869:Gene Expression Profiling; D005947:Glucose / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019194:Ischemic Preconditioning; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
D018696:Neuroprotective Agents; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I; D005947:Glucose; D010100:Oxygen