Journal of Applied Physiology Journal of Applied Physiology
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J Appl Physiol 91: 173-182, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 1, 173-182, July 2001

Molecular adaptations in human skeletal muscle to endurance training under simulated hypoxic conditions

M. Vogt1, A. Puntschart1, J. Geiser2, C. Zuleger2,dagger, R. Billeter1, and H. Hoppeler1

1 Institute of Anatomy, University of Bern, 3012 Bern; and 2 Institute of Physiology, University of Fribourg, 1700 Fribourg, Switzerland

This study was performed to explore changes in gene expression as a consequence of exercise training at two levels of intensity under normoxic and normobaric hypoxic conditions (corresponding to an altitude of 3,850 m). Four groups of human subjects trained five times a week for a total of 6 wk on a bicycle ergometer. Muscle biopsies were taken, and performance tests were carried out before and after the training period. Similar increases in maximal O2 uptake (8.3-13.1%) and maximal power output (11.4-20.8%) were found in all groups. RT-PCR revealed elevated mRNA concentrations of the alpha -subunit of hypoxia-inducible factor 1 (HIF-1) after both high- (+82.4%) and low (+78.4%)-intensity training under hypoxic conditions. The mRNA of HIF-1alpha 736, a splice variant of HIF-1alpha newly detected in human skeletal muscle, was shown to be changed in a similar pattern as HIF-1alpha . Increased mRNA contents of myoglobin (+72.2%) and vascular endothelial growth factor (+52.4%) were evoked only after high-intensity training in hypoxia. Augmented mRNA levels of oxidative enzymes, phosphofructokinase, and heat shock protein 70 were found after high-intensity training under both hypoxic and normoxic conditions. Our findings suggest that HIF-1 is specifically involved in the regulation of muscle adaptations after hypoxia training. Fine-tuning of the training response is recognized at the molecular level, and with less sensitivity also at the structural level, but not at global functional responses like maximal O2 uptake or maximal power output.

hypoxia training; gene expression; oxygen sensor system


dagger Deceased.




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