Identification of Transcription Factors Expressed in Pulmonary Epithelium in Response to Oxygen Tension Shift

点击翻译按钮获取中文摘要

Molecular oxygen (O2) is essential for aerobic organisms. Exposure of tissues or cells to hypoxia induces a variety of adaptive or pathogenic responses. To understand the mechanism and processes of cellular response to hypoxia, we exposed fetal rat lung fibroblasts to hypoxia (pO2=5Pa) and screened the hypoxia-responsible gene by the differential display method. Exposure of the cells to hypoxia activated the phosphoglycerate mutase B (PGM-B) and prolyl 4-hydroxylase (P4H) alpha gene, resulting in the induction of PGM enzymatic activity, concomitant with elevations of PGM-B mRNA and protein levels. The mRNA level was elevated linearly with decreases in partial O2 pressure, indicating a 2-3 fold increase in these levels after 16 h hypoxia. Up-regulation of PGM mRNA by hypoxia was obvious after 8 h exposure, reached its peak after 16 h, persists for 40 h and returned to the basal level after reoxygenation at 20% O2 for 16 h. Run-on and stability assays indicated that PGM-B expression is regulated mainly at the transcriptional step. These results suggest that the induction of PGM-B may contribute to the regulation of glycolytic flux under reduced O2 tension and play a role in the adaptation of cells to hypoxia.