PMID- 22811423
OWN - NLM
STAT- MEDLINE
DCOM- 20120925
LR  - 20220408
IS  - 1522-1210 (Electronic)
IS  - 0031-9333 (Print)
IS  - 0031-9333 (Linking)
VI  - 92
IP  - 3
DP  - 2012 Jul
TI  - Adaptive and maladaptive cardiorespiratory responses to continuous and 
      intermittent hypoxia mediated by hypoxia-inducible factors 1 and 2.
PG  - 967-1003
LID - 10.1152/physrev.00030.2011 [doi]
AB  - Hypoxia is a fundamental stimulus that impacts cells, tissues, organs, and 
      physiological systems. The discovery of hypoxia-inducible factor-1 (HIF-1) and 
      subsequent identification of other members of the HIF family of transcriptional 
      activators has provided insight into the molecular underpinnings of oxygen 
      homeostasis. This review focuses on the mechanisms of HIF activation and their 
      roles in physiological and pathophysiological responses to hypoxia, with an 
      emphasis on the cardiorespiratory systems. HIFs are heterodimers comprised of an 
      O(2)-regulated HIF-1alpha or HIF-2alpha subunit and a constitutively expressed HIF-1beta 
      subunit. Induction of HIF activity under conditions of reduced O(2) availability 
      requires stabilization of HIF-1alpha and HIF-2alpha due to reduced prolyl hydroxylation, 
      dimerization with HIF-1beta, and interaction with coactivators due to decreased 
      asparaginyl hydroxylation. Stimuli other than hypoxia, such as nitric oxide and 
      reactive oxygen species, can also activate HIFs. HIF-1 and HIF-2 are essential 
      for acute O(2) sensing by the carotid body, and their coordinated transcriptional 
      activation is critical for physiological adaptations to chronic hypoxia including 
      erythropoiesis, vascularization, metabolic reprogramming, and ventilatory 
      acclimatization. In contrast, intermittent hypoxia, which occurs in association 
      with sleep-disordered breathing, results in an imbalance between HIF-1alpha and 
      HIF-2alpha that causes oxidative stress, leading to cardiorespiratory pathology.
FAU - Prabhakar, Nanduri R
AU  - Prabhakar NR
AD  - Institute for Integrative Physiology and Center for Systems Biology of O2 
      Sensing, Biological Sciences Division, University of Chicago, Chicago, Illinois, 
      USA. nanduri@uchicago.edu
FAU - Semenza, Gregg L
AU  - Semenza GL
LA  - eng
GR  - R01 HL076537/HL/NHLBI NIH HHS/United States
GR  - HL-86493/HL/NHLBI NIH HHS/United States
GR  - P01-HL-65608/HL/NHLBI NIH HHS/United States
GR  - U54 CA143868/CA/NCI NIH HHS/United States
GR  - HL-76537/HL/NHLBI NIH HHS/United States
GR  - R01-HL-55338/HL/NHLBI NIH HHS/United States
GR  - U54-CA-143868/CA/NCI NIH HHS/United States
GR  - P01 HL025830/HL/NHLBI NIH HHS/United States
GR  - P01 HL090554/HL/NHLBI NIH HHS/United States
GR  - P20 GM078494/GM/NIGMS NIH HHS/United States
GR  - P01 HL065608/HL/NHLBI NIH HHS/United States
GR  - P20-GM-78494/GM/NIGMS NIH HHS/United States
GR  - HL-90554/HL/NHLBI NIH HHS/United States
GR  - R01 HL086493/HL/NHLBI NIH HHS/United States
GR  - HHS-N268201000032C/PHS HHS/United States
GR  - R01 HL055338/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
PL  - United States
TA  - Physiol Rev
JT  - Physiological reviews
JID - 0231714
RN  - 0 (Basic Helix-Loop-Helix Transcription Factors)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 138391-32-9 (Aryl Hydrocarbon Receptor Nuclear Translocator)
RN  - 1B37H0967P (endothelial PAS domain-containing protein 1)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Adaptation, Physiological
MH  - Animals
MH  - Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism
MH  - Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism
MH  - Blood Vessels/metabolism/physiopathology
MH  - Cardiovascular Diseases/*etiology/genetics/metabolism/physiopathology/prevention 
      & control
MH  - Carotid Body/metabolism
MH  - Erythropoiesis
MH  - Gene Expression Regulation
MH  - Humans
MH  - Hypoxia/*complications/genetics/metabolism/physiopathology
MH  - Hypoxia-Inducible Factor 1/genetics/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Ischemic Preconditioning, Myocardial
MH  - Oxidative Stress
MH  - Oxygen/blood
MH  - Pulmonary Ventilation
MH  - Respiration Disorders/*etiology/genetics/metabolism/physiopathology
MH  - Signal Transduction
PMC - PMC3893888
MID - NIHMS523779
EDAT- 2012/07/20 06:00
MHDA- 2012/09/26 06:00
PMCR- 2014/01/16
CRDT- 2012/07/20 06:00
PHST- 2012/07/20 06:00 [entrez]
PHST- 2012/07/20 06:00 [pubmed]
PHST- 2012/09/26 06:00 [medline]
PHST- 2014/01/16 00:00 [pmc-release]
AID - 92/3/967 [pii]
AID - 10.1152/physrev.00030.2011 [doi]
PST - ppublish
SO  - Physiol Rev. 2012 Jul;92(3):967-1003. doi: 10.1152/physrev.00030.2011.