PMID- 26391197
OWN - NLM
STAT- MEDLINE
DCOM- 20161019
LR  - 20161230
IS  - 1469-445X (Electronic)
IS  - 0958-0670 (Linking)
VI  - 101
IP  - 1
DP  - 2016 Jan
TI  - Skeletal muscle hypoxia-inducible factor-1 and exercise.
PG  - 28-32
LID - 10.1113/EP085318 [doi]
AB  - Reduced oxygen levels in skeletal muscle during exercise are a consequence of 
      increased oxygen consumption. The cellular response to hypoxia is conferred to a 
      large extent by activation of the hypoxia-sensitive transcription factor 
      hypoxia-inducible factor-1 (HIF-1). The target genes of HIF-1 increase oxygen 
      transport through mechanisms such as erythropoietin-mediated erythropoiesis and 
      vascular endothelial growth factor-induced angiogenesis and improve tissue 
      function during low oxygen availability through increased expression of glucose 
      transporters and glycolytic enzymes, which makes HIF-1 an interesting candidate 
      as a mediator of skeletal muscle adaptation to endurance training. However, HIF-1 
      may also inhibit cellular oxygen consumption and mitochondrial oxidative 
      metabolism, features discordant with the phenotype of a trained muscle. Skeletal 
      muscle readily adjusts to altered functional demands. Adaptation of skeletal 
      muscle to long-term aerobic training enables better aerobic performance at higher 
      intensities through improved metabolic capacity and oxygen supply. The components 
      of acute exercise that act as triggers for adaptation are still largely unknown; 
      however, an early hypothesis was that local hypoxia acts as a possible stimulus 
      for exercise adaptation. The hypoxia-sensitive subunit, HIF-1alpha, is stabilized in 
      skeletal muscle in response to an acute bout of endurance exercise. However, 
      long-term endurance exercise seems to attenuate the acute HIF-1alpha response. This 
      attenuation is concurrent with an increase in expression of several negative 
      regulators of the HIF system. We propose that the HIF-1alpha response is blunted in 
      response to long-term exercise training through induction of its negative 
      regulators and that this inhibition enables the enhanced oxidative metabolism 
      that is part of a local physiological response to exercise.
CI  - (c) 2015 The Authors. Experimental Physiology (c) 2015 The Physiological Society.
FAU - Lindholm, Malene E
AU  - Lindholm ME
AD  - Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Rundqvist, Helene
AU  - Rundqvist H
AD  - Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, 
      Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20151015
PL  - England
TA  - Exp Physiol
JT  - Experimental physiology
JID - 9002940
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
SB  - IM
MH  - Animals
MH  - Exercise/*physiology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism/*physiology
MH  - Muscle, Skeletal/*metabolism/*physiology
MH  - Physical Conditioning, Animal/physiology
EDAT- 2015/09/24 06:00
MHDA- 2016/11/12 06:00
CRDT- 2015/09/23 06:00
PHST- 2015/07/21 00:00 [received]
PHST- 2015/09/15 00:00 [accepted]
PHST- 2015/09/23 06:00 [entrez]
PHST- 2015/09/24 06:00 [pubmed]
PHST- 2016/11/12 06:00 [medline]
AID - 10.1113/EP085318 [doi]
PST - ppublish
SO  - Exp Physiol. 2016 Jan;101(1):28-32. doi: 10.1113/EP085318. Epub 2015 Oct 15.