Cell selective induction and transcriptional activation of immediate early genes by hypoxia

• Published in: Brain research 1995-10, Vol.697 (1), p.266-270
• Main Authors: Prabhakar, Nanduri R., Shenoy, Bhami C., Simonson, Michael S., Cherniack, Neil S.
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; c- fos; Cattle; Cell Hypoxia; Fibroblast; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Regulation; Genes, fos; Genes, Immediate-Early; Hypoxia; Immediate early response gene; Molecular and cellular biology; Molecular genetics; Nerve growth factor; Neuroblastoma cell; Oxygen - physiology; PC12 Cells; Pheochromocytoma-12 cell; Promoter Regions, Genetic; Rats; RNA, Messenger - metabolism; Rodentia; Transcriptional Activation; Tumor Cells, Cultured
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/0006-8993(95)00994-2

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.