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

Abstract

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 O(2) 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 O(2) uptake or maximal power output.

Critical determinants of combined sprint and endurance performance: an integrative analysis from muscle fiber to the human body

“…Angiogenesis is induced by up-regulation of the VEGF, which occurs with exercise [for review (76)], especially during high-intensity training in hypoxic conditions (77). High-intensity training in hypoxia also increases mRNA expression of Mb (77), likely because of local tissue hypoxia within the muscle. However, hypoxia also attenuates the rate of translation and may result in muscle atrophy [for review (78)].…”

Hypoxia and Resistance Exercise: A Comparison of Localized and Systemic Methods

“…Enhanced metabolic function (i.e. molecular and structural adaptations favoring oxygen transport and utilization) has also been demonstrated following high-intensity cycling training in hypoxia, compared to training in normoxia [115,116], with muscle adaptations being dependent on the degree of hypoxia and the duration of exposure [117]. Given that the localized hypoxic environment created by BFR enhances both acute [8, Researchers have recently begun to investigate the use of hypoxic devices, which typically provide a systemic normobaric hypoxic environment via nitrogen dilution or oxygen extraction [118].…”

A globin in every cell?

“…The possibility that HIF-1 might generally be involved in the induction of Mb is supported by two observations. First, stimulation of the HIF-1 pathway in muscle is triggered by exercise with or without hypoxia and mechanical stress (stretching) (6,10,11). Second, the HIF-1͞Mb system is colocalized in oxidative skeletal myofibers (type I and IIA fibers) (4,12).…”