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Hypoxia-induced expression of phosphoglycerate mutase B in fibroblasts
Y Takahashi1, S Takahashi, T Yoshimi
1Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. yuji@ls.toyaku.ac.jp
Abstract:
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.