Peroxynitrite as an alternative donor of oxygen in HIF-1alpha proline hydroxylation under low oxygen availability.

Sumbayev, V. and Yasinksa, I.M. (2006) Peroxynitrite as an alternative donor of oxygen in HIF-1alpha proline hydroxylation under low oxygen availability. Free Radical Research, 40 (6). pp. 631-635. ISSN 1071-5762. (The full text of this publication is not available from this repository)

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Abstract

In the last years, nitric oxide (NO) mediated signaling became an integral component in understanding physiological and pathophysiological processes of cell proliferation, death or cellular adaptation. Among other activities, NO affects multiple targets that allow regulation of gene expression. Recently, NO was found to attenuate accumulation of hypoxia inducible factor-1alpha (HIF-1alpha) under hypoxic conditions because of several mechanisms: redistribution of oxygen toward non-respiratory oxygen-dependent targets (like HIF-1alpha proline hydroxylases--PHDs, which perform hydroxylation of Pro402/564 of HIF-1alpha leading to its proteasomal degradation); in addition, peroxynitrite formed during interactions between NO and mitochondria derived superoxide leads to an increase in cytosolic iron/2-oxoglutarate (2-OG), which required for PHD activation. Here, we propose a hypothesis that peroxynitrite, formed in the cells upon exposure to NO under low oxygen availability, serves as an alternative donor of oxygen for activated PHDs so they can perform HIF-1alpha proline hydroxylation to de-accumulate the protein.

Item Type: Article
Subjects: Q Science
Divisions: Faculties > University wide - Teaching/Research Groups
Depositing User: Vadim Sumbayev
Date Deposited: 16 Mar 2009 11:15
Last Modified: 14 Jan 2010 14:38
Resource URI: http://kar.kent.ac.uk/id/eprint/10042 (The current URI for this page, for reference purposes)
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