Document Detail

Physiological activation of hypoxia inducible factor-1 in human skeletal muscle.
MedLine Citation:
PMID:  15811877     Owner:  NLM     Status:  MEDLINE    
The human hypoxia inducible factor 1 (HIF-1) system is activated under various pathological conditions, yet less is known about its physiological regulation in healthy human tissue. We have studied the effect of exercise on the activation of HIF-1 in human skeletal muscle. Employing a model where oxygen consumption increases and oxygen tension can be manipulated, nine healthy male subjects performed 45 min of one-legged knee-extension exercise. Biopsies were taken before, directly after, and 30, 120, and 360 min after exercise. Exercise led to elevated HIF-1alpha protein levels and a more prevalent nuclear staining of HIF-1alpha. Interestingly, a concurrent decrease in von Hippel-Lindau tumor suppressor protein (VHL) levels was detected in some subjects. Moreover, exercise induced an increase in the DNA binding activity of HIF-1alpha. Characterization of gene expression by real-time PCR demonstrated that the HIF-1 target genes VEGF and EPO were activated. VEGF mRNA was further increased when blood flow to the exercising leg was restricted. In conclusion, these data clearly demonstrate that physical activity induces the HIF-1-mediated signaling pathway in human skeletal muscle, providing the first evidence that human HIF-1alpha can be activated during physiologically relevant conditions.
Helene Ameln; Thomas Gustafsson; Carl Johan Sundberg; Kensaku Okamoto; Eva Jansson; Lorenz Poellinger; Yuichi Makino
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-04-05
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  19     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2005 Jun 
Date Detail:
Created Date:  2005-05-30     Completed Date:  2006-02-17     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1009-11     Citation Subset:  IM    
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
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MeSH Terms
Basic Helix-Loop-Helix Transcription Factors
DNA / metabolism
Electrophoretic Mobility Shift Assay
Erythropoietin / genetics
Exercise / physiology
Hypoxia-Inducible Factor 1 / analysis,  physiology*
Hypoxia-Inducible Factor 1, alpha Subunit / analysis,  genetics,  physiology*
Muscle, Skeletal / chemistry,  physiology*
Oxygen Consumption
RNA, Messenger / analysis
Signal Transduction / physiology
Transcription Factors / analysis
Vascular Endothelial Growth Factor A / genetics
Von Hippel-Lindau Tumor Suppressor Protein / analysis,  genetics
Reg. No./Substance:
0/Basic Helix-Loop-Helix Transcription Factors; 0/HIF1A protein, human; 0/Hypoxia-Inducible Factor 1; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/RNA, Messenger; 0/Transcription Factors; 0/Vascular Endothelial Growth Factor A; 0/endothelial PAS domain-containing protein 1; 11096-26-7/Erythropoietin; 9007-49-2/DNA; EC protein, human; EC Hippel-Lindau Tumor Suppressor Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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