Scientific Publications by FDA Staff
Biochem Biophys Res Commun 2011 Dec 16;416(3-4):421-6
Inactivation of prolyl hydroxylase domain (PHD) protein by epigallocatechin (EGCG) stabilizes hypoxia-inducible factor (HIF-1alpha) and induces hepcidin (Hamp) in rat kidney.
Manalo DJ, Baek JH, Buehler PW, Struble E, Abraham B, Alayash AI
HIF-1alpha plays a key role in iron uptake and transport in the liver, whose activity is tightly linked to the repression of hepcidin (Hamp). Hamp prevents intestinal iron uptake and cellular efflux by negatively modulating ferroportin. Hamp is also expressed in the kidneys, where transcriptional control by HIF-1alpha remains poorly understood. We show that the administration of epigallocatechin gallate (EGCG) results in a considerable Hamp expression in rat kidneys. We also provide evidence to show that EGCG inhibited prolyl hydroxylase (PHD) activity, essential for HIF-1alpha degradation in vivo and in vitro. Rats that were dosed with EGCG (60mg/kg, intraperitoneal) over a 7day time course stabilized HIF-1alpha protein in kidney tissues. Interestingly, Hamp gene expression was induced, even after subjecting rats to a 4h hypoxia treatment (8% oxygen). Using Hep3B cells, we determined that EGCG conferred its inhibitory action by complexing with PHD, altering its catalytic iron center and thus preventing HIF-1alpha hydroxylation. These data demonstrate EGCG's therapeutic potential in modulating hepcidin expression in diseases associated with altered iron metabolism.
|Category: Journal Article|
|PubMed ID: #22138393||DOI: 10.1016/j.bbrc.2011.11.085|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-12-06||Entry Last Modified: 2012-08-29|