title: [Selected, biochemical markers of hypoxia].
abstract: Although tissues may exist regardless of reduced oxygen pressure, this requires glycolytic ATP generation, which is very expensive from the energetic viewpoint. Hypoxia is defined as the condition in which oxygen pressure is reduced at the level of bodily tissues. There are many clinical situations during which decreased tissue oxygenation may occur. It may be transient or chronic, as well as systemic or local. An emergent need exists for monitoring and diagnosis with respect to numerous possible clinical circumstances leading to hypoxia and its life-threatening consequences. The assessment of global oxygen homeo-stasis relies on blood gas analysis and lactate concentration, but such an approach does not fully reflect the local oxygenation of tissues. Oxygen needle microelectrode measurements reveal great differences in tissue pO2 levels. Local pO2 levels depend on many factors, among which the most important are: the distance to the nearest capillary, the extracellular and intracellular fluid diffusion rates and intracellular measurements of the number and activity levels of mitochondria. Thus, nowadays, it is impossible to establish an accurate normal value ranges for local tissue pO2. Oxygen deficiency is an important gene regulator. A sequence-specific DNA-binding factor, the hypoxia induced factor (HIF), is the fundamental hypoxia response protein. 70 genes identified so far have been found to be HIF-dependent. They are responsible for increased oxygen delivery, i.e. by boosting angiogensis due to vascular endothelial growth factor (VEGF) release and the enhancement of red blood cell production by erythropoietin (EPO). VEGF-induced angiogenesis is one of several key hypoxia adaptations. An enhanced vascular bed in response to hypoxia affects almost every bodily tissue and organ. This was observed particularly in skeletal muscles as well as in the brain. The expression of a few hypoxia markers does not require HIF activation. An especially interesting member of this group is osteopontin (OPN), whose synthesis increases during hypoxia. OPN was originally linked to bone remodeling, but currently it seems to posses an important role in immunity, inflammation and tumor pathogenesis. Quantification of hypoxia is clinically essential both for therapy and prognosis. Taking account of the fact that the concept of oxygen pressure at the tissue level is not quantitative (norms do not exist, results are incomparable), biochemical markers are preferable. Particularly significant in this context are hypoxia-induced proteins such as HIF, EPO, VEGF or potentially OPN.
authors: Zakład Biofizyki i Fizjologii Człowieka WUM, Warszawa. przemyslaw.kwasiborski@wum.edu.pl
authors: Przemysław Jerzy
authors: PJ
authors: Kwasiborski
authors: Paweł
authors: P
authors: Kowalczyk
authors: Piotr
authors: P
authors: Mrówka
authors: Michał
authors: M
authors: Kwasiborski
authors: Andrzej
authors: A
authors: Cwetsch
authors: Jacek
authors: J
authors: Przybylski
mesh_terms: D000222:Adaptation, Physiological; D015415:Biomarkers / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology; D004921:Erythropoietin / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000175:diagnosis* / Q000378:metabolism*; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051793:Hypoxia-Inducible Factor 1; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D004921:Erythropoietin; D010100:Oxygen