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Hypoxia-inducible factors (HIFs) are transcription factors that respond to decreases in available oxygen in the cellular environment, or hypoxia. [1] [2] They also respond to instances of pseudohypoxia, such as thiamine deficiency. [3] [4] Both hypoxia and pseudohypoxia leads to impairment of adenosine triphosphate (ATP) production by the ...
Erythropoietin (/ ɪ ˌ r ɪ θ r oʊ ˈ p ɔɪ. ɪ t ɪ n,-r ə-,-p ɔɪ ˈ ɛ t ɪ n,-ˈ iː t ɪ n /; [1] [2] [3] EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow.
Endothelial PAS domain-containing protein 1 (EPAS1, also known as hypoxia-inducible factor-2alpha (HIF-2α)) is a protein that is encoded by the EPAS1 gene in mammals. It is a type of hypoxia-inducible factor, a group of transcription factors involved in the physiological response to oxygen concentration.
Hypoxia-inducible factor 1-alpha, also known as HIF-1-alpha, is a subunit of a heterodimeric transcription factor hypoxia-inducible factor 1 that is encoded by the HIF1A gene. [ 5 ] [ 6 ] [ 7 ] The Nobel Prize in Physiology or Medicine 2019 was awarded for the discovery of HIF.
Fig. 1 Achieving maximum aerobic capacity. Blood doping is defined as the use of illicit products (e.g. erythropoietin (EPO), darbepoetin-alfa, hypoxia-inducible factor (HIF) stabilizers) and methods (e.g. increase aerobic capacity by maximizing the uptake of O 2) in order to enhance the O 2 transport of the body to the muscles.
From 2000 to 2006, EPO tests at the Olympics were conducted on both blood and urine. [30] [31] However, several compounds have been identified that can be taken orally to stimulate endogenous EPO production. Most of the compounds stabilize the hypoxia-inducible transcription factors which activate the EPO gene. The compounds include oxo ...
Hypoxia may be classified as either generalized, affecting the whole body, or local, affecting a region of the body. [2] Although hypoxia is often a pathological condition, variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise.
Kaelin's research found that in VHL subjects, there are genes that express the formation of a protein critical in the EPO process, but which the mutation suppressed. Kaelin's work aligned with that of Peter J. Ratcliffe and Gregg Semenza who separately had identified a two-part protein, hypoxia-inducible factors (HIF) that was essential to EPO ...