Global gene expression profiling of ischemic preconditioning inthe rat retina

[摘要] Purpose: To obtain and analyze the gene expression changes afterischemic preconditioning (IPC) in the rat retina.Methods: Ischemic damage to the inner retina can be prevented by ashort, non-deleterious, ischemic insult of 5 min applied 24 h precedinga full ischemic insult of 60 min; a phenomenon termed tolerance or IPC.The time course of changes in gene expression after induction of IPC wasassessed by 22K oligonucleotide microarrays, followed by real-timequantitative polymerase chain reaction (qPCR) validation. Functionalpathways of interest were identified by Gene Ontology-term analysis.Results: Histology confirmed that IPC induction by 5 min of retinalischemia results in a complete protection against the neurodegenerativeeffects of a 60 min ischemic period applied 24 or 48 h later. Themicroarray analysis revealed differential expression of 104 known genesat one or more time points between 1 h and 7 days after IPC. The groupof altered genes contained a significant overrepresentation of genesinvolved in aminoacyl-tRNA synthetase activity (Iars, Lars,Cars, Yars, Gars, Tars), amino acid transport(Slc3a2, Slc6a6, Slc7a1, Slc38a2), regulation oftranscription (including Egr1, Egr4, Nr4a1, Nr4a3,c-fos), and cell death (including Anxa1, Trib3). qPCR assayson cDNA of individual animals confirmed the microarray results.Conclusions: Endogenous neuroprotection, provoked by ischemicpreconditioning is associated with changes in transcript levels ofseveral functionally-related groups of genes. During the time window ofeffective protection, transcript levels of genes encoding foraminoacyl-tRNA synthetases and for amino acid transport are reduced.These changes suggest that a reduction of translational activity mayplay a significant role in preconditioning-mediated neuroprotection.

[学科分类] 生物化学/生物物理