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

分子氧(O2)对好氧生物是必不可少的。组织或细胞暴露在低氧环境中会引起各种适应性或致病反应。为了了解细胞对低氧反应的机制和过程，我们将胎鼠肺成纤维细胞暴露于低氧(pO2=5PA)中，并通过差异显示的方法筛选与低氧相关的基因。细胞暴露于低氧条件下，磷酸甘油酸变位酶B(PGM-B)和脯氨基4-羟基酶(P4H)α基因被激活，导致PGM酶活性的诱导，并伴随着PGM-B基因和蛋白水平的升高。随着氧分压的降低，mRNA水平呈线性上升，表明低氧16h后，这些水平增加了2-3倍。缺氧后8h，PGM-B的表达明显上调，16h达到高峰，持续40h，复氧16h后恢复到基础水平，Run-on和稳定性分析表明，PGM-B的表达主要在转录水平调节。这些结果表明，PGM-B的诱导可能有助于调节低氧下的糖酵解通量，并在细胞对低氧的适应中发挥作用。

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.