Skip to main content
Kent Academic Repository

Nitric oxide inhibits HIF-1alpha protein accumulation under hypoxic conditions: implication of 2-oxoglutarate and iron.

Kozhukhar, Anna V., Yasinska, Inna M., Sumbayev, Vadim V. (2006) Nitric oxide inhibits HIF-1alpha protein accumulation under hypoxic conditions: implication of 2-oxoglutarate and iron. Biochimie, 88 (5). pp. 411-18. ISSN 0300-9084. (doi:10.1016/j.biochi.2005.09.007) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided) (KAR id:10039)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided.
Official URL:
http://dx.doi.org/10.1016/j.biochi.2005.09.007

Abstract

Cells exposed to low oxygen conditions respond by initiating defense mechanisms, including the stabilization of hypoxia-inducible factor (HIF) 1alpha, a transcription factor that upregulates genes such as those involved in angiogenesis and glycolysis, which also plays a pivotal role in the regulation of cellular utilization of oxygen and is an essential regulator of angiogenesis in solid tumor and ischemic disorders. Nitric oxide and other inhibitors of mitochondrial respiration prevent the stabilization of HIF-1alpha during hypoxia. In the present study we found that nitric oxide inhibits HIF-1alpha accumulation under low oxygen (1%) conditions. The effect is supported by an increase in 3-nitrotyrosine and is more likely caused by the formation of peroxynitrite in the cells, which leads to the damage of mitochondria and their respiratory chain followed by the increase in 2-oxoglutarate (2-OG) and iron (the components needed to activate HIF-1alpha proline hydroxylases) concentrations in cell cytosol. The inhibiting effect of NO on HIF-1alpha accumulation was not observed in the cells lacking mitochondria. On the other hand the depletion of intracellular glutathione (GSH) was observed upon cell treatment with nitric oxide donors under hypoxic conditions. Treatment of those cells with N-acetyl cysteine (NAC) increased the amount of intracellular GSH and attenuated the NO effect and abolished the damage of mitochondria as well as 2-OG/iron release.

Item Type: Article
DOI/Identification number: 10.1016/j.biochi.2005.09.007
Subjects: Q Science
Divisions: Divisions > Division of Natural Sciences > Medway School of Pharmacy
Depositing User: Vadim Sumbayev
Date Deposited: 16 Mar 2009 11:11 UTC
Last Modified: 16 Nov 2021 09:48 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/10039 (The current URI for this page, for reference purposes)

University of Kent Author Information

  • Depositors only (login required):

Total unique views for this document in KAR since July 2020. For more details click on the image.