Intermittent hypoxia-mediated plasticity of acute O2 sensing requires altered red-ox regulation by HIF-1 and HIF-2.
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.
Center for Systems Biology of O Sensing, Department of Medicine, University of Chicago, Chicago, IL 60637, USA. nanduri@uchicago.edu
Nanduri R
NR
Prabhakar
Ganesh K
GK
Kumar
Jayasri
J
Nanduri
D000313:Adrenal Medulla / Q000166:cytology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism / Q000502:physiology*; D001794:Blood Pressure; D002344:Carotid Body / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism*; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D051793:Hypoxia-Inducible Factor 1; D010100:Oxygen; D000099162:Endothelial PAS Domain-Containing Protein 1