HIF and VEGF relationships in response to hypoxia and sciatic nerve stimulation in rat gastrocnemius.
To determine if hypoxia-inducible factor-1 (HIF-1) may regulate skeletal muscle vascular endothelial growth factor (VEGF) expression in response to exercise or hypoxia, rats underwent 1h sciatic nerve electrical stimulation (ES), hypoxic exposure (H) or combined stimuli. HIF-1alpha protein levels increased six-fold with maximal (8V) ES with or without H. Similar HIF-1alpha increases occurred with sub-maximal (6V and 4V) ES plus H, but not in sub-maximal ES or H alone. VEGF mRNA and protein levels increased three-fold in sub-maximal ES or H alone, six-fold in sub-maximal ES plus H, 6.3-fold with maximal ES, and 6.5-fold after maximal ES plus H. These data suggest: (1) intracellular hypoxia during normoxic exercise may exceed that during 8% oxygen breathing at rest and is more effective in stimulating HIF-1alpha; (2) HIF-1 may be an important regulator of exercise-induced VEGF transcription; and (3) breathing 8% O(2) does not alter HIF-1alpha expression in skeletal muscle, implying that exercise-generated signals contribute to the regulation of HIF-1alpha and/or VEGF.
Tang
Kechun
K
Division of Physiology (0623A), Department of Medicine, University of California at San Diego, La Jolla, CA 92093, USA. ktang@ucsd.edu
Breen
Ellen C
EC
Wagner
Harrieth
H
Brutsaert
Tom D
TD
Gassmann
Max
M
Wagner
Peter D
PD
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004558:Electric Stimulation; D005260:Female; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012584:Sciatic Nerve / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; C497444:Hif1a protein, rat; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A