Oxygen sensors in the organism: examples of regulation under altitude hypoxia in mammals.
Oxygen sensing is a determinant function of mammals, especially humans, to maintain their activity under acute or chronic exposure to hypoxia. True O2 sensors (chemoreceptors, erythropoietin secreting cells) are involved in regulation loops, which aim to restore O2 availability to the cells. Pseudo O2 sensors are cells activated by the lack of oxygen but not clearly involved in regulation processes. Potassium channels in the carotid bodies have been suspected to be O2 sensitive and could mediate the chemosensitivity to hypoxia. Na,K-ATPase related ion transport in alveolar pneumocytes could be sensitive to O2 availability and regulate the flux of water and sodium in the alveolar space. Signal transduction in G-protein-dependent receptor systems is modified in hypoxia, such as in cardiac beta-receptors and adenosinergic and muscarinic receptors. Recent studies have provided some evidence to the possible role of hypoxia inducible factors (HIF-1) in the regulation of protein synthesis at the transcriptional level. Similarities between O2-sensing mechanisms in erythropoiesis and in the synthesis of vascular endothelial growth factor were recently evidenced. Both genes are upregulated in hypoxia. However, the precise structure (heme-linked enzyme?) of all these O2-sensitive sites is not known, either in the erythropoietic system or in the chemoreceptor function. An adequate balance between hypoxia-induced upregulation and downregulation processes is necessary for optimal survival in a hypoxic environment.
Richalet
J P
JP
Laboratoire de Physiologie, Association pour la Recherche en Physiologie de l'Environnement, U.F.R. Médecine, Bobigny, France.
D000531:Altitude; D000818:Animals; D002118:Calcium / Q000378:metabolism; D015536:Down-Regulation; D004920:Erythropoiesis; D004921:Erythropoietin / Q000502:physiology; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D008322:Mammals; D010100:Oxygen / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000378:metabolism; D015854:Up-Regulation
D010281:Parathyroid Hormone; D004921:Erythropoietin; D010100:Oxygen; D002118:Calcium