Abstract | PURPOSE: To obtain and analyze the gene expression changes after ischemic preconditioning (IPC) in the rat retina. METHODS: Ischemic damage to the inner retina can be prevented by a short, non-deleterious, ischemic insult of 5 min applied 24 h preceding a full ischemic insult of 60 min; a phenomenon termed tolerance or IPC. The time course of changes in gene expression after induction of IPC was assessed by 22K oligonucleotide microarrays, followed by real-time quantitative polymerase chain reaction (qPCR) validation. Functional pathways of interest were identified by Gene Ontology-term analysis. RESULTS: Histology confirmed that IPC induction by 5 min of retinal ischemia results in a complete protection against the neurodegenerative effects of a 60 min ischemic period applied 24 or 48 h later. The microarray analysis revealed differential expression of 104 known genes at one or more time points between 1 h and 7 days after IPC. The group of altered genes contained a significant overrepresentation of genes involved in aminoacyl-tRNA synthetase activity (Iars, Lars, Cars, Yars, Gars, Tars), amino acid transport (Slc3a2, Slc6a6, Slc7a1, Slc38a2), regulation of transcription (including Egr1, Egr4, Nr4a1, Nr4a3, c-fos), and cell death (including Anxa1, Trib3). qPCR assays on cDNA of individual animals confirmed the microarray results. CONCLUSIONS: Endogenous neuroprotection, provoked by ischemic preconditioning is associated with changes in transcript levels of several functionally-related groups of genes. During the time window of effective protection, transcript levels of genes encoding for aminoacyl- tRNA synthetases and for amino acid transport are reduced. These changes suggest that a reduction of translational activity may play a significant role in preconditioning-mediated neuroprotection.
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Authors | W Kamphuis, F Dijk, S van Soest, A A B Bergen |
Journal | Molecular vision
(Mol Vis)
Vol. 13
Pg. 1020-30
(Jun 28 2007)
ISSN: 1090-0535 [Electronic] United States |
PMID | 17653046
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Amino Acid Transport Systems
- Heat-Shock Proteins
- RNA, Messenger
- Amino Acyl-tRNA Synthetases
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Topics |
- Amino Acid Transport Systems
(genetics)
- Amino Acyl-tRNA Synthetases
(genetics)
- Animals
- Cell Death
(genetics)
- Cytoprotection
(genetics)
- Gene Expression Profiling
- Heat-Shock Proteins
(genetics)
- Ischemia
(complications)
- Ischemic Preconditioning
- Male
- Microarray Analysis
- Neurodegenerative Diseases
(etiology, prevention & control)
- RNA, Messenger
(metabolism)
- Rats
- Rats, Wistar
- Retinal Vessels
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
- Time Factors
- Transcription, Genetic
(physiology)
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