• Home
  •  > Scopus Publication Detail

Scopus Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in Scopus. This abstract is what is used to create the fingerprint of the publication.


Mutual antagonism between hypoxia-inducible factors 1α and 2α regulates oxygen sensing and cardio-respiratory homeostasis

Guoxiang Yuan; Ying-Jie Peng; Vaddi Damodara Reddy; Vladislav V. Makarenko; Jayasri Nanduri; Shakil A. Khan; Joseph A. Garcia; Ganesh K. Kumar; Gregg L. Semenza; Nanduri R. Prabhakar

(Profiled Author: Joseph A Garcia)

Proceedings of the National Academy of Sciences of the United States of America. 2013;110(19):E1788-E1796.

Abstract

Breathing and blood pressure are under constant homeostatic regulation to maintain optimal oxygen delivery to the tissues. Chemosensory reflexes initiated by the carotid body and catecholamine secretion from the adrenal medulla are the principalmechanisms for maintaining respiratory and cardiovascular homeostasis; however, the underlying molecular mechanisms are not known. Here, we report that balanced activity of hypoxia-inducible factor-1 (HIF-1) and HIF-2 is critical for oxygen sensing by the carotid body and adrenalmedulla, and for their control of cardio-respiratory function. In Hif2α+/- mice, partial HIF-2α deficiency increased levels of HIF-1α and NADPH oxidase 2, leading to an oxidized intracellular redox state, exaggerated hypoxic sensitivity, and cardio-respiratory abnormalities, which were reversed by treatment with a HIF-1α inhibitor or a superoxide anion scavenger. Conversely, in Hif1α+/- mice, partial HIF-1α deficiency increased levels of HIF-2α and superoxide dismutase 2, leading to a reduced intracellular redox state, blunted oxygen sensing, and impaired carotid body and ventilatory responses to chronic hypoxia, which were corrected by treatment with a HIF-2α inhibitor. None of the abnormalities observed in Hif1α+/- mice or Hif2α+/- mice were observed in Hif1α+/-;Hif2α+/- mice. These observations demonstrate that redox balance, which is determined bymutual antagonism between HIF-α isoforms, establishes the set point for hypoxic sensing by the carotid body and adrenal medulla, and is required for maintenance of cardiorespiratory homeostasis.


PMID: 23610397     PMCID: PMC3651442    

Scientific Context

This section shows information related to the publication - computed using the fingerprint of the publication - including related publications, related experts with fingerprints representing significant amounts of overlap between their fingerprint and this publication. The red dots indicate whether those experts or terms appear within the publication, thereby showing potential and actual connections.

Related Publications

Related Topics

Appears in this Publication Appears in this Document

Related Experts

Author of this Publication Author of this Document