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Expression of c‐ fos and c‐ jun family genes after focal cerebral ischemia
Author(s) -
An Gang,
Lin TengNan,
Liu JiaShou,
Xue JuanJuan,
He YongYue,
Hsu Chung Y.
Publication year - 1993
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410330508
Subject(s) - ischemia , cerebral cortex , middle cerebral artery , cerebral blood flow , cortex (anatomy) , c jun , in situ hybridization , gene expression , c fos , cerebral infarction , medicine , endocrinology , transcription factor , chemistry , biology , gene , neuroscience , biochemistry
The expression of the protooncogenes, c‐ fos , jun B, c‐ jun , and jun D was investigated in a rat focal cerebral ischemia model by Northern analysis and in situ hybridization. Severe ischemia (reduction of regional blood flow by 88‐92%) in this model is confined to cerebral cortex irrigated by the right middle cerebral artery. Ischemia for 30 minutes, which caused only slight cortical damage (infarct size, <10 mm 3 ), induced both jun B and c‐ fos mRNAs exclusively in the right cerebral cortex. Ischemia for 90 minutes, which led to large cortical infarction (infarct size, >140 mm 3 ), also induced the expression of these two genes in the right cerebral cortex as well as the ipsilateral hippocampus. The latter sustained very mild ischemia (reduction of regional blood flow by 10–20%). The coinduction of jun B and c‐ fos expression occurred immediately after reperfusion and peaked at 60 minutes after reperfusion. The expression of c‐ jun was enhanced in a similar pattern, but at a much lower magnitude. In contrast, no change in jun D expression was observed. Nuclear run‐on assays indicated that the increase in c‐ fos , jun B, and c‐ jun mRNA levels was due to the increase of transcription rate in these genes. Mobility shift assays showed a basal DNA binding activity of transcription factor AP‐1 in the right cerebral cortex. Ischemia for 30 or 90 minutes followed by reperfusion for 4 hours resulted in a four‐ to sixfold increase of AP‐1 binding activity. The enhanced DNA binding activity persisted for as long as 24 hours, These results suggest that the enhanced expression of AP‐1, a general transcription factor, may play a role in the alteration of gene regulation in the ischemic cortex.