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

Yung-Ting Kuo, Jhong-Huei Jheng, Mei-Chen Yang, Wei-Lu Chen, Shyang-Guang Wang, Horng-Mo Lee

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Abstract

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. 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 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.

Original languageEnglish
Pages (from-to)1-201
Number of pages201
JournalFree Radical Research
DOIs
Publication statusE-pub ahead of print - May 15 2018

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Hypoxia-Inducible Factor 1
Energy Metabolism
Pyruvic Acid
Prolyl-Hydroxylase Inhibitors
Oxidoreductases
Phosphorylation
Hexokinase
Facilitative Glucose Transport Proteins
Mitochondrial Membrane Potential
Mitochondrial Proteins
Glycolysis
Electron Transport Complex IV
Lung Neoplasms
Proteins
Iron
Adenosine Triphosphate
Cells
A549 Cells
Hypoxia
Oxygen

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Ferrous glycinate regulates cell energy metabolism by restricting hypoxia-induced factor-1α expression in human A549 cells. / Kuo, Yung-Ting; Jheng, Jhong-Huei; Yang, Mei-Chen; Chen, Wei-Lu; Wang, Shyang-Guang; Lee, Horng-Mo.

In: Free Radical Research, 15.05.2018, p. 1-201.

Research output: Contribution to journalArticle

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AU - Chen, Wei-Lu

AU - Wang, Shyang-Guang

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AB - 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. 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 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.

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