HIF-1: a key mediator in hypoxia.

ABSTRACT

The transcription factor HIF-1 is one of the principal mediators of homeostasis in human tissues exposed to hypoxia. It is implicated in virtually every process of rapid gene expression in response to low oxygen levels. The most common causes of tissue hypoxia are inflammation and/or insufficient circulation or a combination of both. Inflamed tissues and the areas surrounding malignant tumors are characterized by hypoxia and low concentrations of glucose. Serious and generalized inflammation can lead to sepsis and circulatory collapse resulting in acute or chronic tissue hypoxia in various vital organs which induces a rapid homeostatic process in all nucleated cells of affected organs in the human body. Under hypoxic conditions the alpha and beta subunits of HIF-1 make an active heterodimer and drive the transcription of over 60 genes important for cell survival, adaptation, anaerobic metabolism, immune reaction, cytokine production, vascularization and general tissue homeostasis. In addition, HIF-1 plays a key role in the development of physiological systems in fetal and postnatal life. It is also a critical mediator of cancer, lung and cardiovascular diseases. The better understanding of the functions of HIF-1 and the pharmacological modulation of its activity could mean a successful therapeutic approach to these diseases.