Page last updated: 2024-10-24

cellular response to hyperoxia

Definition

Target type: biologicalprocess

Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating increased oxygen tension. [GOC:mah]

Cellular response to hyperoxia is a complex process involving multiple signaling pathways and cellular adaptations to protect against the damaging effects of excessive oxygen. Hyperoxia, defined as an abnormally high concentration of oxygen, can lead to oxidative stress, DNA damage, and cell death. To counteract these adverse effects, cells employ a variety of mechanisms, including:

1. **Antioxidant defense:** Cells increase the production of antioxidant enzymes like superoxide dismutase (SOD), catalase, and glutathione peroxidase, which neutralize reactive oxygen species (ROS) generated by hyperoxia.
2. **Protein folding and repair:** Hyperoxia can disrupt protein folding and lead to misfolded proteins. Cells respond by increasing chaperone protein production, which helps in proper protein folding and repair.
3. **Transcriptional regulation:** Hyperoxia triggers specific gene expression changes, leading to the synthesis of proteins involved in antioxidant defense, DNA repair, and cell survival.
4. **Cellular signaling pathways:** Signaling pathways like the NF-κB, Nrf2, and MAPK pathways are activated in response to hyperoxia, mediating various cellular responses, including inflammation, antioxidant gene expression, and cell survival.
5. **Mitochondrial adaptation:** Mitochondria, the powerhouse of the cell, are particularly vulnerable to hyperoxia. Cells adapt by increasing mitochondrial biogenesis, enhancing the efficiency of mitochondrial respiration, and modulating mitochondrial membrane permeability to minimize ROS production.
6. **Cell cycle arrest and apoptosis:** In cases of severe hyperoxia, cells can undergo programmed cell death (apoptosis) or arrest the cell cycle to prevent the propagation of damaged cells.

These cellular responses to hyperoxia are interconnected and work in concert to maintain cellular homeostasis. However, the extent of these responses and the success of the protective mechanisms can vary depending on the severity and duration of hyperoxia exposure, as well as the cellular context and individual differences.'
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Proteins (2)

ProteinDefinitionTaxonomy
Forkhead box protein O1A forkhead box protein O1 that is encoded in the genome of human. [PRO:PD]Homo sapiens (human)
Ubiquitin-like modifier-activating enzyme ATG7A ubiquitin-like modifier-activating enzyme ATG7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O95352]Homo sapiens (human)

Compounds (3)

CompoundDefinitionClassesRoles
psammaplysene apsammaplysene A: dimeric bromotyrosine alkaloid; specific inhibitor of FOXO1a nuclear export; structure in first source
pevonedistatpevonedistat : A pyrrolopyrimidine that is 7H-pyrrolo[2,3-d]pyrimidine which is substituted by a (1S)-2,3-dihydro-1H-inden-1-ylnitrilo group at position 4 and by a (1S,3S,4S)-3-hydroxy-4-[(sulfamoyloxy)methyl]cyclopentyl group at position 7. It is a potent and selective NEDD8-activating enzyme inhibitor with an IC50 of 4.7 nM, and currently under clinical investigation for the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes.

pevonedistat: a potent and selective inhibitor of NAE (NEDD8-activating enzyme)
cyclopentanols;
indanes;
pyrrolopyrimidine;
secondary amino compound;
sulfamidate
antineoplastic agent;
apoptosis inducer
as 18428565-amino-7-(cyclohexylamino)-1-ethyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid: inhibits Foxo1 transactivation; inhibits mRNA levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase; structure in first source

AS1842856 : A quinolone that is 4-quinolone substituted at positions 1, 3, 5, 6 and 7 by ethyl, carboxy, amino, fluorine, and cyclohexylamino groups, respectively. It can directly bind to and block the transcription activity of the active forkhead box protein O1 (Foxo1), but not the Ser256-phosphorylated form. It induces cell death and growth arrest in Burkitt lymphoma cell lines at low concentrations.
organofluorine compound;
primary amino compound;
quinolinemonocarboxylic acid;
quinolone;
secondary amino compound;
tertiary amino compound
anti-obesity agent;
antineoplastic agent;
apoptosis inducer;
autophagy inhibitor;
forkhead box protein O1 inhibitor;
hypoglycemic agent