HIF-1 and ventilatory acclimatization to chronic hypoxia.
Ventilatory acclimatization to hypoxia (VAH) is a time-dependent increase in ventilation and ventilatory O2-sensitivity that involves plasticity in carotid body chemoreceptors and CNS respiratory centers. Hypoxia inducible factor-1alpha (HIF-1alpha) controls the expression of several genes that increase physiological O2 supply. Studies using transgenic mice show HIF-1alpha expression in the carotid bodies and CNS with chronic sustained and intermittent hypoxia is important for VAH. Other O2-sensitive transcription factors such as HIF-2alpha may be important for VAH by reducing metabolic O2 demands also. Specific gene targets of HIF-1alpha shown to be involved in VAH include erythropoietin, endothelin-1, neuronal nitric oxide synthase and tyrosine hydroxylase. Other HIF-1alpha targets that may be involved in VAH include vascular endothelial growth factor, heme oxygenase 1 and cytoglobin. Interactions between these multiple pathways and feedback control of HIF-1alpha expression from some of the targets support a complex and powerful role for HIF-1alpha in neural plasticity of physiological control circuits with chronic hypoxia.
Powell
Frank L
FL
Department of Medicine and White Mountain Research Station, University of California, San Diego, La Jolla, CA 92093-0623, USA. fpowell@ucsd.edu
Fu
Zhenxing
Z
D000064:Acclimatization / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002908:Chronic Disease; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology*; D051793:Hypoxia-Inducible Factor 1 / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D012123:Pulmonary Ventilation / Q000502:physiology*
D051793:Hypoxia-Inducible Factor 1