High-density DNA microarray analysis of gene expression following transient focal cerebral ischemia in mouse

Hou, Sheng T.; Becker, Kevin G.; Baggley, Anne; Chen, Gao; Webster, Jacqueline

doi:10.1016/s0531-5131(03)00023-2

Cited by 1 publication

(2 citation statements)

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“…Although focal cerebral ischemia, such as the mouse model used in the present study, appears to produce a localized focal lesion on the ipsilateral side of the brain, based on gross pathological parameters, increasing genomic evidence indicates that altered gene expression also occurs on the contralateral side of the brain (17,27). It is therefore not surprising to see a relatively smaller increase in E2F1 binding to the contralateral side of the ischemic brain on the EMSA (Fig.…”

Section: Discussionmentioning

confidence: 67%

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Neuropilin-1 Is a Direct Target of the Transcription Factor E2F1 during Cerebral Ischemia-Induced Neuronal Death In Vivo

Jiang

Sheldrick

Desbois

et al. 2007

Molecular and Cellular Biology

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The nuclear transcription factor E2F1 plays an important role in modulating neuronal death in response to excitotoxicity and cerebral ischemia. Here, by comparing gene expression in brain cortices from E2F1 ؉/؉ and E2F1 ؊/؊ mice using a custom high-density DNA microarray, we identified a group of putative E2F1 target genes that might be responsible for ischemia-induced E2F1-dependent neuronal death. Neuropilin 1 (NRP-1), a receptor for semaphorin 3A-mediated axon growth cone collapse and retraction, was confirmed to be a direct target of E2F1 based on (i) the fact that the NRP-1 promoter sequence contains an E2F1 binding site, (ii) reactivation of NRP-1 expression in E2F1 ؊/؊ neurons when the E2F1 gene was replaced, (iii) activation of the NRP-1 promoter by E2F1 in a luciferase reporter assay, (iv) electrophoretic mobility gel shift analysis confirmation of the presence of an E2F binding sequence in the NRP-1 promoter, and (v) the fact that a chromatin immunoprecipitation assay showed that E2F1 binds directly to the endogenous NRP-1 promoter. Interestingly, the temporal induction in cerebral ischemia-induced E2F1 binding to the NRP-1 promoter correlated with the temporal-induction profile of NRP-1 mRNA, confirming that E2F1 positively regulates NRP-1 during cerebral ischemia. Functional analysis also showed that NRP-1 receptor expression was extremely low in E2F1 ؊/؊ neurons, which led to the diminished response to semaphorin 3A-induced axonal shortening and neuronal death. An NRP-1 selective peptide inhibitor provided neuroprotection against oxygenglucose deprivation. Taken together, these findings support a model in which E2F1 targets NRP-1 to modulate axonal damage and neuronal death in response to cerebral ischemia.

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Section: Discussionmentioning

confidence: 67%

“…The spot intensity was subtracted from the background signals, and the intensities of the four repeats were averaged. The z ratio was calculated, and changes in the z ratio between ischemia and sham were calculated using the following formula as described previously (17):…”

Section: Methodsmentioning

confidence: 99%