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Title 

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

Authors 

E A ChoH K SongS H LeeBong Hyun ChungH M LimMyung Kyu Lee

Publisher 

Wiley-Blackwell

Issue Date 

2013

Citation 

Journal of Cellular Biochemistry, vol. 114, no. 4, pp. 864-873

Keywords 

HIF HYDROXYLASESHYDROXYLASE INHIBITIONHYPOXIA INDUCIBLE FACTORIRON CHELATORS

Abstract 

Hypoxia inducible factor 1α (HIF-1α), an essential transcriptional factor, is negatively regulated by two different types of oxygen and Fe2+-dependent HIF hydroxylases, proline hydroxylase (PHD) and factor inhibiting HIF (FIH), under normoxia. Iron chelators have therefore been used for inducing HIF-1α expression by inhibiting the hydroxylases. In this study, the iron chelators displayed differential effects for PHD and FIH in cells depending on their iron specificity and membrane permeability rather than their in vitro potencies. The membrane permeability of the strict Fe 2+-chelator potentially inhibited both hydroxylases, whereas the membrane impermeable one showed no inhibitory effect in cells. In contrast, the depletion of the extracellular Fe3+ ion was mainly correlated to PHD inhibition, and the membrane permeable one elicited low efficacy for both enzymes in cells. The 3′-hydroxyl group of quercetin, a natural flavonoid, was critical for inhibition of intracellular hydroxylases. Since the 3′-methylation of quercetin is induced by catechol-O-methyl transferase, the enzyme may regulate the intracellular activity of quercetin. These data suggest that the multiple factors of iron-chelators may be responsible for regulating the intracellular activity HIF hydroxylases.

ISSN 

0730-2312

Link 

http://dx.doi.org/10.1002/jcb.24423

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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