HIF and VEGF relationships in response to hypoxia and sciatic nerve stimulation in rat gastrocnemius

Kechun Tang, Ellen C. Breen, Harrieth Wagner, Tom D. Brutsaert, Max Gassmann, Peter D. Wagner

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

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 1 h sciatic nerve electrical stimulation (ES), hypoxic exposure (H) or combined stimuli. HIF-1α protein levels increased six-fold with maximal (8 V) ES with or without H. Similar HIF-1α increases occurred with sub-maximal (6 V and 4 V) 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-1α; (2) HIF-1 may be an important regulator of exercise-induced VEGF transcription; and (3) breathing 8% O2 does not alter HIF-1α expression in skeletal muscle, implying that exercise-generated signals contribute to the regulation of HIF-1α and/or VEGF.

Original languageEnglish (US)
Pages (from-to)71-80
Number of pages10
JournalRespiratory Physiology and Neurobiology
Volume144
Issue number1
DOIs
StatePublished - Nov 30 2004
Externally publishedYes

Keywords

  • Exercise
  • HIF-1
  • Hypoxia
  • Mammals
  • Modulators
  • Muscle
  • Rat
  • Skeletal
  • Skeletal muscle
  • VEGF
  • VEGF expression

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology
  • Pulmonary and Respiratory Medicine

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