The Human Oxygen Sensing Machinery and Its Manipulation

Animals respond to the challenge of limited oxygen availability by a coordinated response that works to increase oxygen supply and minimize tissue damage. The chronic hypoxic response is mediated by the alpha,beta-hypoxia inducible transcription factor (HIF) that enables the expression of a gene array. Because this array includes genes encoding for proteins that regulate processes including red blood cell and blood vessel formation, manipulation of the HIF system has potential for the treatment of ischemic diseases, anaemia and tumours. Hydroxylase enzymes act as oxygen sensors by regulating both the lifetime of HIF-alpha and its transcriptional activity. This tutorial review aims to provide a non-expert introduction to the HIF field by providing a background to current work, summarising molecular knowledge on the HIF system, and outlining opportunities for therapeutic intervention.