Hypoxia-lnducible Factor 1

Hypoxia-lnducible Factor 1From Molecular Biology to Cardiopulmonary Physiology
Hypoxia-inducible factor 1 (HIF-1) accumulates in the nuclei of mammalian cells exposed to reduced 02 tension in a time- and 02 concentration-dependent manner. HIF-1 plays an important role in 02 homeostasis by activating transcription of genes whose products mediate essential cellular and systemic responses to hypoxia, including erythropoiesis (erythropoietin), glycolysis (glucose transporter-1, aldolase A, enolase 1, lactate dehydrogenase A, phosphofructokinase L, and phosphoglycerate kinase 1), vasculogenesis (vascular endothelial growth factor), and vasodilation (inducible nitric oxide synthase and heme oxygenase 1). Recent studies suggest that HIF-1 represents a vital link between 02 sensing, gene transcription, and physiological adaptation to chronic hypoxia in vivo. canada viagra

Systemic and Cellular Physiologic Responses to Hypoxia
The response to hypoxia is complex and is determined by the nature of the inciting stimulus. Only a few of the many homeostatic adaptations will be described herein (Table 1). A lowlander who flies from Baltimore to Aspen, Colo, and takes a gondola ride to the top of Aspen Mountain (11,000 feet) will undergo a variety of physiologic adaptations to maintain homeostasis in the presence of approximately one third less 02 in the inspired air. Under these conditions, the stimulus is chronic in nature (as long as the lowlander remains at high altitude), and as in the case of any chronic stimulus (lasting longer than a few minutes), the responses involve changes in gene expression. One of the classic adaptations to hypobaric hypoxia is an increased rate of erythropoiesis that is mediated by the glycoprotein growth factor/hormone erythropoietin (EPO). EPO is produced by peritubular interstitial cells in the kidney that sense 02 tension and respond to hypoxia by increasing transcription of the EPO gene. In addition to representing a hazard of recreational travel, systemic hypoxia is also a feature of more ominous medical conditions, including those associated with the following: decreased 02 exchange, such as COPDs; decreased cardiac output, such as cardiomyopathy and congestive heart failure; and right-to-left circulatory shunts, such as congenital heart disease and pulmonary hypertension.
Table 1—Cellular and Systemic Homeostatic Responses to Hypoxia Mediated by HIF-1

Response Gene Product
Erythropoiesis Erythropoietin (EPO)
Glycolysis Aldolase A (ALDA)
Enolase 1 (ENOl)
Glucose transporter-1 (GLUT1)
Lactate dehydrogenase A (LDHA)
Phosphofructokinase L (PFKL)
Phosphoglycerate kinase 1 (PGK1)
Vasodilation Inducible nitric oxide synthase (iNOS)
Heme oxygenase-1 (HOI)
Angiogenesis Vascular endothelial growth factor (VEGF)

Category: Hypoxia

Tags: dna-binding activity, hypoxia-response element, protein hif-1