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

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. 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.

Keywords:

• Hypoxia
• ferrous glycinate
• Warburg effect
• mitochondrial energy metabolism

Acknowledgement

The authors thanked Yu-Ting Hsueh for technical assistances with the Western blot.

Disclosure statement

The authors declare that there is no conflict of interest, financial or otherwise in this study.

References

Additional information

Funding

This work was supported by the research grant from the Ministry of Science and Technology [MOST106-2320-B-038-043 for H. M. L.]. This work was supported by the research grant from the Ministry of Science and Technology [MOST104-2320-B-038-064, MOST106-2320-B-038-043 for H. M. L.].