Overexpression of genes in the CA1 hippocampus region of adult rat following episodes of global ischemia.
Ischemic stress is associated with marked changes in gene expression in the hippocampus--albeit little information exists on the activation of nonabundant genes. We have examined the expression of several known genes and identified novel ones in the adult rat hippocampus after a mild, transient, hypovolemic and hypotensive, global ischemic stress. An initial differential screening using a prototype array to assess gene expression after stress followed by a suppression subtractive hybridization protocol and cDNA microarray revealed 124 nonoverlapped transcripts predominantly expressed in the CA1 rat hippocampus region in response to ischemic stress. About 78% of these genes were not detected with nonsubtracted probes. Reverse transcription polymerase chain reaction (RT-PCR) and in situ hybridization on these 124 transcripts confirmed the differential expression of at least 83. Most robustly expressed were gene sequences NFI-B, ATP1B1, RHOGAP, PLA2G4A, BAX, CASP3, P53, MAO-A, FRA1, HSP70.2, and NR4A1 (NUR77), as well as sequence tags of unknown function. New stress-related genes of similar functional motifs were identified, reemphasizing the importance of functional grouping in the analysis of multiple gene expression profiles. These data indicate that ischemia elicits expression of an array of functional gene clusters that may be used as an index for stress severity and a template for target therapy design.
Department of Neurobiology, The Weizmann Institute of Science, Rehovot 76100, Israel.
E
E
Yakubov
M
M
Gottlieb
S
S
Gil
P
P
Dinerman
P
P
Fuchs
E
E
Yavin
D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D002546:Ischemic Attack, Transient / Q000235:genetics / Q000378:metabolism*; D008297:Male; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; C539820:Nr4a1 protein, rat; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53