EPO promotes erythropoiesis in the bone marrow and thereby improves oxygen

Epo promotes erythropoiesis in the bone marrow and

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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
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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
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