Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxygen is crucial to aerobic metabolism, but excesses of oxygen or reactive oxygen species (ROS) can injure cells. This minireview addresses two transcription factors that regulate several cellular responses to oxygen tension. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric protein activated by hypoxia. Levels of HIF-1 are regulated by removal of the HIF-1alpha subunit through ubiquination and proteasomal destruction under normoxic conditions. Hypoxia inhibits the ubiquination of HIF-1alpha, preventing its destruction and allowing it to bind to hypoxia-responsive elements in gene promoter, enhancer, and intronic sequences. HIF-1 induces the expression of the hypoxia responsive genes vascular endothelial growth factor and erythropoietin. Its dysregulation has been implicated in von Hippel-Lindau disease. Nuclear factor kappaB (NFkappaB) is a family of pleotropic, dimeric transcription factors, and has a complex pattern of regulation. Under normoxic conditions, NFkappaB is bound to one of several inhibitory proteins (e.g., IkappaB) that prevent its nuclear translocation. Hyperoxia or elevations of ROS cause the ubiquination and destruction of the inhibitory proteins, freeing NFkappaB and allowing it to bind to target gene promoters. Hyperoxia in cell and animal models and acute lung injury in humans induce the expression of multiple proinflammatory cytokines through NFkappaB-dependent mechanisms. Although HIF-1 and NFkappaB respond to changes in pO(2), the precise nature of the oxygen sensing and transduction pathways is unclear in both cases. Both heme-protein and redox-sensitive mechanisms have been proposed. Improved understanding of oxygen-sensitive gene regulation may suggest targeted therapies for human disease.
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PMID:Oxygen regulation of gene expression: a study in opposites. 1100 29

A decline in the tissue oxygen level below normal leads to cellular hypoxia. This situation is very frequently encountered in solid tumors as existing blood vessels cannot satisfy the requirements in oxygen of the rapidly growing tumor. Like hyperoxia, hypoxia is a stress factor for cells and tissues. Adapting to this stressful situation leads to activation of the dimeric transcription factor hypoxia-inducible factor-1 (HIF-1) that induces gene expression in promoting tumor cell survival. In addition, hypoxia acts as a selection factor for radio- and chemotherapy resistant tumor cells with a high potential of malignancy. Consequently, over expression of the HIF-1alpha subunit is associated with an advanced disease stage and poor prognosis of cancer patients. During the last few years intense effort has been made in investigating natural compounds that can be used as HIF-1 inhibitors. These compounds aim to suppress tumor hypoxia and to increase the susceptibility of tumor cells to radio- and chemo-therapy. In this review we summarize recent findings concerning HIF-1 regulation and present a survey of HIF-1 inhibiting natural compounds that have been discovered in the last few years.
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PMID:Natural compounds and the hypoxia-inducible factor (HIF) signalling pathway. 1970 12