Takahashi Y, Takahashi S, Yoshimi T, Miura T
Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.
Eur J Biochem. 1998 Jun 15;254(3):497-504. doi: 10.1046/j.1432-1327.1998.2540497.x.
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 approximately 5 Pa) and screened the hypoxia-responsible gene by the differential display method. Exposure of the cells to hypoxia activated the phosphoglycerate mutase B (PGM-B) 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, persisting 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 the glycolytic flux under reduced O2 tension and play a role in the adaptation of cells to hypoxia.
分子氧（O₂）对需氧生物至关重要。组织或细胞暴露于缺氧环境会引发多种适应性或致病性反应。为了解细胞对缺氧反应的机制和过程，我们将胎鼠肺成纤维细胞暴露于缺氧环境（pO₂约为5 Pa），并通过差异显示法筛选与缺氧相关的基因。细胞暴露于缺氧环境会激活磷酸甘油酸变位酶B（PGM-B）基因，导致PGM酶活性升高，同时PGM-B mRNA和蛋白质水平也会升高。mRNA水平随氧分压降低呈线性升高，表明缺氧16小时后这些水平会增加2-3倍。暴露于缺氧环境8小时后，PGM mRNA的上调明显，16小时后达到峰值，持续40小时，在20% O₂复氧16小时后恢复到基础水平。核转录分析和稳定性分析表明，PGM-B的表达主要在转录水平受到调控。这些结果表明，PGM-B的诱导可能有助于在低氧张力下调节糖酵解通量，并在细胞对缺氧的适应中发挥作用。
