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

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 pheochrom ocytoma-12 (PC-12), hepatoblastoma (Hep3B), neuroblastoma and fibrobla st 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, He p3B, and fibroblasts but not in neuroblastoma cells. Significant induc tion of c-fos mRNA was seen with hypoxic exposure as short as 15 min a nd the effects persisted at 10 h of low pO2 exposure. Hypoxia stimulat ed transcription from a 356 bp fragment of the c-fos promoter linked t o a choloramphenicol acetyl transferase reporter in PC-12 but not in n euroblastoma cells. Fetal bovine serum, however, activated c-fos promo ter both in PC-12 and neuroblastoma cells. These results demonstrate c ell type selective mechanisms for c-fos promoter activation that requi re nucleic acid sequences with in the first 356 bp of the c-fos promot er. These observations suggest that increased IERG transcription is on e of the early events in genomic adaptations to hypoxia.