CELL SELECTIVE INDUCTION AND TRANSCRIPTIONAL ACTIVATION OF IMMEDIATE-EARLY GENES BY HYPOXIA

被引:49
作者
PRABHAKAR, NR [1 ]
SHENOY, BC [1 ]
SIMONSON, MS [1 ]
CHERNIACK, NS [1 ]
机构
[1] CASE WESTERN RESERVE UNIV,DEPT MED,CLEVELAND,OH 44106
关键词
HYPOXIA; IMMEDIATE EARLY RESPONSE GENE; C-FOS; PHEOCHROMOCYTOMA-12; CELL; NERVE GROWTH FACTOR; NEUROBLASTOMA CELL; FIBROBLAST;
D O I
10.1016/0006-8993(95)00994-2
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
c-fos and jun belong to the immediate early response genes (ERG) that initiate phenotypic changes in response to a variety of extracellular stimuli In the present study, we examined whether hypoxia induces IERG expression in isolated cells. Experiments were performed on pheochromocytoma-12 (PC-12), hepatoblastoma (Hep3B), neuroblastoma and fibroblast cells that were exposed either to normoxia (21% O2) or to hypoxia (5% O2) for one hour. mRNAs for c-fos, c-jun, junB, junD were analyzed by northern blot assay. Increases in IERG mRNAs were seen in PC-12, Hep3B, and fibroblasts but not in neuroblastoma cells. Significant induction of c-fos mRNA was seen with hypoxic exposure as short as 15 min and the effects persisted at 10 h of low pO2 exposure. Hypoxia stimulated transcription from a 356 bp fragment of the c-fos promoter linked to a choloramphenicol acetyl transferase reporter in PC-12 but not in neuroblastoma cells. Fetal bovine serum, however, activated c-fos promoter both in PC-12 and neuroblastoma cells. These results demonstrate cell type selective mechanisms for c-fos promoter activation that require nucleic acid sequences with in the first 356 bp of the c-fos promoter. These observations suggest that increased IERG transcription is one of the early events in genomic adaptations to hypoxia.
引用
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页码:266 / 270
页数:5
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