RESUMO
The erythropoietin(EPO) system was used to study the molecular mechanisms associated with the induction of hypoxia responsive genes and from these investigations the hypoxia-inducible factors (HIFs) was identified as a key transcriptional hypoxic regulator of EPO. Subsequent research has now found that a large number of other hypoxia-inducible genes are also induced by HIF under hypoxic conditions. The HIF transcriptional complex is a heterodimer consisting of an alpha subunit and a beta subunit. Recently, two oxygen sensor, oxygen-dependent prolyl and asparaginyl hydroxylation were found,and it is the first time that the oxygen sensor had been described for higher organisms. This review focused on the structure and functions of HIF and the regulation of HIF proteins by hypoxia and oxygen sensors.
RESUMO
Oxygen is a mandatory for all aerobic organisms. Oxygen-containing free radicals are produced when oxygen is not completely reduced to water in energy-producing oxidation reaction.The radicals may also transform into other reactive compounds through electron transfer and all the compounds with similar functions are referred as reactive oxygen species(ROS).Increased ROS is known to cause damage to proteins,DNA and lipids.Much evidence showed that changes in partial oxygen pressure,hormone,cytokine and chemical stimulation could increase ROS,and ROS,acting as signaling molecules,mediates cell functions.Hypoxia-inducing factor(HIF),a key transcriptional factor for most hypoxia-inducible genes,is a heterodimer consisting of 2 subunits.Recent study found that ROS plays an important role in HIF activity regulation under hypoxic and non-hypoxic conditions.This paper reviews the production of ROS and its role in the regulation of HIF activity.