hypoxia, the kidneys produce erythropoietin (EPO). EPO promotes
erythropoiesis in the bone marrow and thereby improves oxygen
carrying capacity in the blood. The production of EPO is promoted by
Hypoxia-Inducible Factor-1 (HIF-1), which protein levels are increased in
skeletal muscle during hypoxia for cellular hypoxia prevent the
catabolism of HIF-1α (Flaherty et al., 2016).
In hypoxic cells is hypoxia inducible factor 1 (HIF-1) present, while in
non-hypoxic cells HIF-1 was not detectable (Semenza, 1999). HIF-1α is
a subunit of HIF-1 and regulated by cellular oxygen levels: under
normoxia HIF-1α is hydroxylated and degraded, while under hypoxia
HIF-1α is stable and translocated to the nucleus. That is why under
hypoxic conditions higher concentrations of HIF-1 are found. HIF-1
appears to play a critical role in cellular and systemic O2-homeostasis
during both development and postnatal life. Different genes with an
hypoxia response element (HRE) seemed to have a higher gene
transcription in cells which were incubated under 1% O2 relative to
expression at 20% O2. (Semenza, 1999)
HIF plays a role in the switch from oxidative to glycolytic metabolism.
This is achieved by the induction of the expression of (1) glucose
transport and glycolytic enzymes, which increases the flux from
glucose to pyruvate. (2) PDK-1, which blocks the conversion form
pyruvate to Acetyl CoA and (3) lactate dehydrogenase A, which
converts pyruvate to lactate. (Kim, Tchernyshyov, Semenza, & Dang,
2006). HIF-1 turns on different transcription genes including genes
responsible for glycolysis, glucose uptake, angiogenesis and the
erythropoietin (EPO) gene. Reduced skeletal muscle HIF-1 seems to
improve the oxidative capacity and endurance performance (Lindholm
& Rundqvist, 2016). For HIF-1 induces (indirect) glycolysis, glucose
uptake and angiogenesis, HIF-1 decreases the oxygen consumption
and increases the oxygen delivery to cells.
Endurance exercise and prolonged stay at high altitude have two
things in common: first of all, both lead to reduced cellular oxygen
levels. Secondly, they both lead to adaptations which increase the
endurance performance. These corresponding effects suggest a
common pathway by which endurance performance is increased. If
high altitude has the same effects as endurance exercise it is plausible
that their muscular adaptations are caused by cellular hypoxia.
In this thesis, the hypothesis that the adaption of muscle metabolism
due to exercise training is caused by cellular hypoxia in the muscle
tissue will be discussed by comparing the effects of high altitude and
exercise training on skeletal muscle. In the first chapter the
adaptations of muscle tissue in response to exercise training will be
discussed and explained, beside that it discusses if there is any
evidence that proves cellular hypoxia will occur in the muscle during
exercise. The second chapter declares which mechanism may lead to
adaptations to cellular hypoxia. In the third chapter the adaptations in
the muscle tissue in response to high altitude will be discussed and
declared. In the fourth chapter some studies that combine endurance
exercise training and high altitude will be discussed. Finally, based on
