Ferrous glycinate regulates cell energy metabolism by restrictinghypoxia-induced factor-1α expression in human A549 cells
| Autor: | Shyang-Guang Wang, Mei-Chen Lo, Wei-Lu Chen, Horng Mo Lee, Jhong-Huei Jheng, Yung Ting Kuo |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
inorganic chemicals
0301 basic medicine Lactate dehydrogenase A Glycine Biochemistry Ferrous 03 medical and health sciences Structure-Activity Relationship 0302 clinical medicine Tumor Cells Cultured Cytochrome c oxidase Humans Ferrous Compounds education A549 cell Membrane Potential Mitochondrial education.field_of_study biology Dose-Response Relationship Drug Chemistry General Medicine TFAM Pyruvate dehydrogenase complex Hypoxia-Inducible Factor 1 alpha Subunit Warburg effect 030104 developmental biology Anaerobic glycolysis A549 Cells 030220 oncology & carcinogenesis biology.protein Energy Metabolism |
| Zdroj: | Free radical research. 52(11-12) |
| ISSN: | 1029-2470 |
| Popis: | Iron or oxygen regulates the stability of hypoxia inducible factor-1α (HIF-1α). We investigated whether ferrous glycinate would affect HIF-1α accumulation, aerobic glycolysis and mitochondrial energy metabolism in human A549 lung cancer cells. Incubation of A549 cells with ferrous glycinate decreased the protein levels of HIF-1α, which was abrogated by proteosome inhibitor, or prolyl hydroxylase inhibitor. The addition of ferrous glycinate decreased protein levels of glucose transporter-1, hexokinase-2, and lactate dehydrogenase A, and decreased pyruvate dehydrogenase kinase-1 (PDK-1) and pyruvate dehydrogenase (PDH) phosphorylation in A549 cells. Ferrous glycinate also increased the expression of the mitochondrial transcription factor A (TFAM), and the mitochondrial protein, cytochrome c oxidase (COX-IV). Silencing of HIF-1α expression mimicked the effects of ferrous glycinate on PDK-1, PDH, TFAM and COX-IV in A549 cells. Ferrous glycinate increased mitochondrial membrane potential and ATP production in A549 cells. These results suggest that ferrous glycinate may reverse Warburg effect through down regulating HIF-1α in A549 cells. |
| Databáze: | OpenAIRE |
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