Nodal regulates energy metabolism in glioma cells by inducing expression of hypoxia-inducible factor 1
| Autor: | Yung Yen Cheng, Li Wen Liu, Chin Cheng Lee, Horng Mo Lee, Jing Huei Lai, Shyang Guang Wang, Hsin I. Ma, Hsun Jin Jan, Dueng-Yuan Hueng |
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| Rok vydání: | 2013 |
| Předmět: |
inorganic chemicals
Cancer Research Nodal Protein Blotting Western macromolecular substances Oxidative phosphorylation Mitochondrion Biology Carbohydrate metabolism chemistry.chemical_compound Adenosine Triphosphate Oxygen Consumption parasitic diseases Tumor Cells Cultured Humans Lactic Acid RNA Small Interfering Hypoxia Luciferases Membrane Potential Mitochondrial Hexokinase Brain Neoplasms food and beverages Glioma Hypoxia-Inducible Factor 1 alpha Subunit Molecular biology Mitochondria Cell biology carbohydrates (lipids) Glucose Oncology Hypoxia-inducible factors chemistry Anaerobic glycolysis Basic and Translational Investigations Cancer cell Phosphorylation Neurology (clinical) Energy Metabolism Glycolysis |
| Zdroj: | Neuro-Oncology. 15:1330-1341 |
| ISSN: | 1523-5866 1522-8517 |
| DOI: | 10.1093/neuonc/not086 |
| Popis: | A shift in glucose metabolism from oxidative phosphorylation to anaerobic glycolysis is the biochemical hallmark of malignant cancer cells.In the present study, we demonstrated that Nodal stimulated the expression of glycolytic enzymes and decreased reliance on mitochondrial oxidative phosphorylation in human glioma cancer cells. The shift in glucose metabolism was mediated by induction of the hypoxia-inducible factor (HIF).Nodal protein expression was shown to be correlated with expression levels of glucose transporter (Glut)-1, hexokinase (HK)-II, pyruvate dehydrogenase kinase (PDK)-1, the phosphorylation level of pyruvate dehydrogenase (PDH), glucose uptake, and lactate accumulation in human glioma cells. These effects were inversely correlated with mitochondrial oxygen consumption and ATP production. Knockdown of Nodal expression with specific small hairpin RNA reduced Glut-1, HK-II, and PDK-1 expressions and PDH phosphorylation. Nodal knockdown also reduced glucose uptake and lactate generation, which in turn increased mitochondrial membrane potential (Ψ), O2 utilization, and ATP synthesis. The ectopic expression of Nodal in low-expressing Nodal glioma cells resulted in the opposite results compared with those of Nodal knockdown glioma cells. Treatment of cells with recombinant Nodal increased HIF-1 expression, and this effect was regulated at the transcriptional level. Blockage of the Nodal receptor by a pharmacological inhibitor or Nodal knockdown in U87MG cells decreased HIF-1α expression. Furthermore, HIF-1α knockdown in U87MG cells decreased Glut-1, HK-II, and PDK-1 expressions and PDH phosphorylation, which were similar to results in Nodal knockdown cells.Taken together, these results suggest that Nodal affects energy metabolism through HIF-1α. |
| Databáze: | OpenAIRE |
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