Hypoxia-induced expression of phosphoglycerate mutase B in fibroblasts.
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.
Laboratory of Environmental Molecular Physiology, School of Life Sciences, Tokyo University of Pharmacy and Life Science, Hachioji, Japan. yuji@ls.toyaku.ac.jp
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Takahashi
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Takahashi
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Yoshimi
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Miura
D000818:Animals; D015687:Cell Hypoxia; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000201:enzymology; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007700:Kinetics; D008928:Mitochondria / Q000187:drug effects; D009687:Nuclear Proteins / Q000378:metabolism; D010736:Phosphoglycerate Mutase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014157:Transcription Factors; D014158:Transcription, Genetic
D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D010736:Phosphoglycerate Mutase