Differential in vitro and cellular effects of iron chelators for hypoxia inducible factor hydroxylases

• DOI: 10.1002/jcb.24423
• Publication Date: 2012-10-23T17:17:45Z
• Authors: Eun A. Cho; Hyun Kyung Song; Sang‐Hyeup Lee; Bong Hyun Chung; Heon Man Lim; Myung Kyu Lee
• Keywords: Hypoxia-Inducible Factors; Membrane permeability

Hypoxia inducible factor 1α (HIF-1α), an essential transcriptional factor, is negatively regulated by two different types of oxygen and Fe(2+) -dependent HIF hydroxylases, proline hydroxylase (PHD) inhibiting (FIH), under normoxia. Iron chelators have therefore been used for inducing HIF-1α expression the hydroxylases. In this study, iron displayed differential effects PHD FIH in cells depending on their specificity membrane permeability rather than vitro potencies. The strict -chelator potentially inhibited both whereas impermeable one showed no inhibitory effect cells. contrast, depletion extracellular Fe(3+) ion was mainly correlated to inhibition, permeable elicited low efficacy enzymes 3'-hydroxyl group quercetin, a natural flavonoid, critical inhibition intracellular Since 3'-methylation quercetin induced catechol-O-methyl transferase, enzyme may regulate activity quercetin. These data suggest that multiple factors iron-chelators be responsible regulating