Cell selective induction and transcriptional activation of immediate early genes by hypoxia.
c-fos and jun belong to the immediate early response genes (IERG) 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.
Prabhakar
N R
NR
Departments of Physiology & Biophysics, Case Western Reserve University, Cleveland, OH 44106, USA.
Shenoy
B C
BC
Simonson
M S
MS
Cherniack
N S
NS
D000818:Animals; D002417:Cattle; D015687:Cell Hypoxia; D005786:Gene Expression Regulation; D017781:Genes, Immediate-Early; D016762:Genes, fos; D010100:Oxygen / Q000502:physiology*; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D010100:Oxygen