Figure 2.
Proposed mechanism of action of DFO. Decreased cellular iron availability after DFO treatment increases VEGF mRNA expression and VEGF protein translation.52 Iron (Fe2+) is a necessary cofactor for PHD, the enzyme responsible for constitutively degrading HIF-1α. By sequestering iron, DFO inactivates PHD resulting in increased HIF-1α accumulation and increased VEGF transcription.53 DFO prevents iron-catalyzed reactive oxygen stress,48 while also reducing free radical formation and resultant cell death.54,55 Figure created with Biorender.com. HIF-1α, hypoxia-inducible factor 1 alpha; DFO, deferoxamine; PHD, prolyl 4-hydroxylase; VEGF, vascular-endothelial growth factor.