Hypoxia and hypoxia-inducible factor in renal disease - PubMed (original) (raw)

Review

doi: 10.1159/000148256. Epub 2008 Jul 30.

Affiliations

Free article

Review

Hypoxia and hypoxia-inducible factor in renal disease

Masaomi Nangaku et al. Nephron Exp Nephrol. 2008.

Free article

Abstract

Tissue hypoxia occurs when local metabolism is disturbed by an imbalance between oxygen supply and consumption. In patients with chronic kidney disease, chronic hypoxia in the kidneys is the end result of multiple processes and mechanisms. Once established, however, accumulating evidence points to this chronic hypoxia as the central player and final common pathway to end-stage renal disease. The cellular response to hypoxia is centered on hypoxia-inducible factor, HIF. This factor is composed of two subunits, an oxygen-sensitive HIF-alpha subunit and a constitutively expressed HIF-beta subunit. Intracellular accumulation of HIF induces the coordinated expression of a number of adaptive genes against hypoxic insult.Three isoforms of HIF-alpha subunits have been identified, HIF-1alpha, HIF-2alpha, and HIF-3alpha, of which HIF-2alpha is involved in the regulation of erythropoietin as well as oxidative stress. HIF is regulated by prolyl hydroxylation and asparaginyl hydroxylation of the HIF-alpha subunit at the protein level. Because HIF is activated only to suboptimal levels in various pathogenic states, therapeutic activation holds promise as a novel and effective approach to the future care of end-stage renal disease.

Copyright (c) 2008 S. Karger AG, Basel.

PubMed Disclaimer

Similar articles

Cited by

Publication types

MeSH terms

Substances

LinkOut - more resources