Ferrous glycinate regulates cell energy metabolism by restrictinghypoxia-induced factor-1α expression in human A549 cells

• Published in: Free radical research Vol. 52; no. 11-12; pp. 1348 - 1358
• Main Authors: Kuo, Yung-Ting, Jheng, Jhong-Huei, Lo, Mei-Chen, Chen, Wei-Lu, Wang, Shyang-Guang, Lee, Horng-Mo
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 02.12.2018
• Subjects: A549 Cells; Dose-Response Relationship, Drug; Energy Metabolism - drug effects; Ferrous Compounds - chemistry; Ferrous Compounds - pharmacology; ferrous glycinate; Glycine - analogs & derivatives; Glycine - chemistry; Glycine - pharmacology; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; Hypoxia-Inducible Factor 1, alpha Subunit - deficiency; Membrane Potential, Mitochondrial - drug effects; mitochondrial energy metabolism; Structure-Activity Relationship; Tumor Cells, Cultured; Warburg effect; Hypoxia; mitochondrial energy metabolism; Warburg effect; ferrous glycinate
• ISSN: 1071-5762; 1029-2470; 1029-2470
• DOI: 10.1080/10715762.2018.1476691

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.