Document Detail

Regular endurance training reduces the exercise induced HIF-1alpha and HIF-2alpha mRNA expression in human skeletal muscle in normoxic conditions.
MedLine Citation:
PMID:  16284786     Owner:  NLM     Status:  MEDLINE    
Regular exercise induces a variety of adaptive responses that enhance the oxidative and metabolic capacity of human skeletal muscle. Although the physiological adjustments of regular exercise have been known for decades, the underlying mechanisms are still unclear. The hypoxia inducible factors 1 and 2 (HIFs) are clearly related heterodimeric transcription factors that consist of an oxygen-depended alpha-subunit and a constitutive beta-subunit. With hypoxic exposure, HIF-1alpha and HIF-2alpha protein are stabilized. Upon heterodimerization, HIFs induce the transcription of a variety of genes including erythropoietin (EPO), transferrin and its receptor, as well as vascular endothelial growth factor (VEGF) and its receptor. Considering that several of these genes are also induced with exercise, we tested the hypothesis that the mRNA level of HIF-1alpha and HIF-2alpha subunits increases with a single exercise bout, and that this response is blunted with training. We obtained muscle biopsies from a trained (5 days/week during 4 weeks) and untrained leg from the same human subject before, immediately after, and during the recovery from a 3 h two-legged knee extensor exercise bout, where the two legs exercised at the same absolute workload. In the untrained leg, the exercise bout induced an increase (P<0.05) in HIF-1alpha fold and HIF-2alpha fold mRNA at 6 h of recovery. In contrast, HIF-1alpha and HIF-2alpha mRNA levels were not altered at any time point in the trained leg. Obviously, HIF-1alpha and HIF-2alpha mRNA levels are transiently increased in untrained human skeletal muscle in response to an acute exercise bout, but this response is blunted after exercise training. We propose that HIFs expression is upregulated with exercise and that it may be an important transcription factor that regulates adaptive gene responses to exercise.
Carsten Lundby; Max Gassmann; Henriette Pilegaard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-11-12
Journal Detail:
Title:  European journal of applied physiology     Volume:  96     ISSN:  1439-6319     ISO Abbreviation:  Eur. J. Appl. Physiol.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-28     Completed Date:  2006-08-31     Revised Date:  2007-04-11    
Medline Journal Info:
Nlm Unique ID:  100954790     Medline TA:  Eur J Appl Physiol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  363-9     Citation Subset:  IM    
Copenhagen Muscle Research Centre, Copenhagen, Denmark.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors / metabolism*
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Muscle, Skeletal / metabolism*
Physical Fitness*
RNA, Messenger / metabolism*
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/RNA, Messenger; 0/endothelial PAS domain-containing protein 1

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