Intermittent hypoxia-mediated plasticity of acute O2 sensing requires altered red-ox regulation by HIF-1 and HIF-2.

Full Abstract

This article provides a brief review of recent studies addressing the effects of chronic intermittent hypoxia (IH) on acute O2 sensing in carotid bodies (CBs) and adrenal medullary chromaffin cells (AMCs) and the underlying mechanisms. Chronic IH upregulates hypoxic sensing ability of CBs and AMCs in adults and neonates. The effects of IH were reversible in adult rats, whereas that of neonatal IH persist into adult life. Reactive oxygen species (ROS) mediate IH-induced changes in O2 sensing. Differential regulation of hypoxia-inducible factors 1 and 2 (HIF-1 and 2) contribute to IH-evoked oxidative stress. HIF-1 activation by IH appears to be linked to increased pro-oxidant(s), whereas downregulation of HIF-2 by IH is coupled to transcriptional downregulation of antioxidant enzyme(s). Thus, the studies with chronic IH suggest novel, hitherto uncharacterized, roles for HIF-1 and HIF-2 in regulating red-ox status leading to plasticity of O2 sensing in CBs and AMCs.

Author information

Author/s: Prabhakar, Nanduri R (NR); Kumar, Ganesh K (GK); Nanduri, Jayasri (J);

Affiliation: Center for Systems Biology of O Sensing, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. nanduri(-atsign-)uchicago.edu

Grants: HL-76537 (Agency:NHLBI NIH HHS) ; HL-86493 (Agency:NHLBI NIH HHS) ; HL-90554 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural; Review

Journal: Annals of the New York Academy of Sciences (Ann N Y Acad Sci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 1177 (issue ) : pp 162-8

Dates: Created 2009/10/22; Completed 2009/11/02;

PMID: 19845618, status: MEDLINE (last retrieval date: 11/2/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adrenal Medulla - cytology
Animals
Anoxia - metabolism; physiopathology
Basic Helix-Loop-Helix Transcription Factors - metabolism; physiology
Blood Pressure

Carotid Body - metabolism
Chromaffin Cells - metabolism
Humans
Hypoxia-Inducible Factor 1 - metabolism; physiology
Oxygen - metabolism

Associated Chemicals: Basic Helix-Loop-Helix Transcription Factors (0) ; Hypoxia-Inducible Factor 1 (0) ; endothelial PAS domain-containing protein 1 (0) ; Oxygen (7782-44-7)

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