PMID- 17705795
OWN - NLM
STAT- MEDLINE
DCOM- 20071015
LR  - 20161124
IS  - 0071-1365 (Print)
IS  - 0071-1365 (Linking)
VI  - 43
DP  - 2007
TI  - Cellular mechanisms associated with intermittent hypoxia.
PG  - 91-104
AB  - Hypoxia, i.e. decreased availability of oxygen occurs under many different 
      circumstances and can be either continuous or intermittent. Continuous hypoxia 
      such as that experienced during periods of high altitude leads to physiological 
      adaptations, whereas chronic IH (intermittent hypoxia) associated with 
      sleep-disordered breathing manifested as recurrent apneas leads to morbidity. The 
      purpose of the present chapter is to highlight recent findings on cellular 
      responses to IH. Studies on cell culture models of IH revealed that for a given 
      duration and intensity, IH is more potent than continuous hypoxia in evoking 
      transcriptional activation. IH activates HIF-1 (hypoxia-inducible factor-1), the 
      immediate early gene c-fos, activator protein-1, nuclear factor kappaB and 
      cAMP-response-element-binding protein. Physiological studies showed that HIF-1 
      plays an important role in chronic IH-induced autonomic abnormalities in mice. IH 
      affects expression of proteins associated with neuronal survival and apoptosis, 
      as well as post-translational modifications of proteins resulting in increased 
      biological activity. Comparisons between continuous hypoxia and IH revealed 
      notable differences in the kinetics of protein kinase activation, type of protein 
      kinase being activated and the downstream targets of protein kinases. IH 
      increases ROS (reactive oxygen species) generation both in cell culture and in 
      intact animals, and ROS-mediated signalling mechanisms contribute to cellular and 
      systemic responses to IH. Future studies utilizing genomic and proteomic 
      approaches may provide important clues to the mechanisms by which IH leads to 
      morbidity as opposed to continuous hypoxia-induced adaptations. Cellular 
      mechanisms associated with IH (other than recurrent apneas) such as repetitive, 
      brief ascents to altitude, however, remain to be studied.
FAU - Nanduri, Jayasri
AU  - Nanduri J
AD  - Center for Systems Biology, Department of Medicine, The University of Chicago, 
      Chicago, IL 60637, USA. nanduri@uchicago.edu
FAU - Nanduri, R Prabhakar
AU  - Nanduri RP
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Essays Biochem
JT  - Essays in biochemistry
JID - 0043306
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.- (Protein Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Enzyme Activation
MH  - Humans
MH  - *Hypoxia/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Mice
MH  - Models, Biological
MH  - NF-kappa B/metabolism
MH  - Neurons/metabolism
MH  - Oxygen/metabolism
MH  - Protein Kinases/metabolism
MH  - Protein Processing, Post-Translational
MH  - Transcriptional Activation
RF  - 51
EDAT- 2007/08/21 09:00
MHDA- 2007/10/16 09:00
CRDT- 2007/08/21 09:00
PHST- 2007/08/21 09:00 [pubmed]
PHST- 2007/10/16 09:00 [medline]
PHST- 2007/08/21 09:00 [entrez]
AID - BSE0430091 [pii]
AID - 10.1042/BSE0430091 [doi]
PST - ppublish
SO  - Essays Biochem. 2007;43:91-104. doi: 10.1042/BSE0430091.