What Is a Hypoxia Inducing Factor?
Hypoxia inducible factor-1 (HIF-1) was first discovered by Semenza and Wang in 1992, and then the structure of HIF-1 was established and its cDNA was proved. Encoding order. HIF-1 is ubiquitous in human and mammalian cells and is also expressed under normal oxygen (21% O2), but the synthetic HIF-1 protein is quickly degraded by the intracellular oxygen-dependent ubiquitin protease degradation pathway. HIF-1 can be stably expressed under hypoxia.
Hypoxia-inducible factor
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- Hypoxia inducible factor-1 (HIF-1) was first discovered by Semenza and Wang in 1992, and then the structure of HIF-1 was established and its cDNA was proved. Encoding order. HIF-1 is commonly found in humans and
- HIF-1 is transcriptionally active
- HIF-1 is a heterodimer mainly composed of 120kD HIF-1 and 91 ~ 94kD HIF-1 subunits. HIF-1
- HIF-1 subunit is stably expressed in cytoplasm, while HIF-1 subunit is degraded by ubiquitin-protease hydrolysis complex after translation. So in normal
- Hypoxia Most species that need oxygen to breathe have
- The following are human HIF families:
| member | gene | protein |
|---|---|---|
| HIF-1 | HIF1A | Hypoxia-inducible factor-1, alpha subunit |
| HIF-1 | HIF-1 | Aromatic hydrocarbon receptor nuclear transfer |
| HIF-2 | EPAS1 | Endothelial PAS domain protein-1 |
| HIF-2 | ARNT2 | Aryl hydrocarbon receptor nuclear transfer-2 |
| HIF-3 | HIF3A | Hypoxia-inducible factor-3, alpha subunit |
| HIF-3 | ARNTL | Aryl hydrocarbon receptor nuclear transfer-3 |
- In cells, the HIF signaling cascade is affected by hypoxia. Under anoxic conditions, cells are usually sustained
- Proline residues on the subunit in HIF are hydroxylated by HIF prolyl hydroxylase, making it capable of being VHL E3
Hypoxia-inducible factor anemia
- Recently, various inhibitors of HIF prolyl hydroxylase have been developed that are selective. Most notable among them are FibroGen's compounds FG-2216 and FG-4592, two drugs that treat [anaemia] orally. By inhibiting HIF prolyl hydroxylase, the stability of HIF-2 in the kidney is increased, which leads to the production of erythropoietin. These two drugs have been successful in phase II clinical trials, but these were suspended in May 2007 because of experimental deaths from fulminant hepatitis. However, it is unclear whether hepatitis deaths were caused by FG-2216. In early 2008, the suspension of clinical trials was lifted due to review and approval by the US FDA.
Hypoxia-inducible factor inflammation and cancer
- In other cases, follow the treatment topic above. Recent studies have shown that inducing HIF expression under normoxic conditions may cause diseases with chronic inflammatory components. And it has been shown that chronic inflammation is self-perpetuating and is the result of abnormal activation of transcription factors due to abnormalities in the microenvironment. Occurs in cells, and changes in the balance of growth factors, chemokines, cytokines, and reactive oxygen species, in turn, provide the need for growth, causing cancer to occur and metastasize. Recently published findings include many disorders, including imbalances of NF-B and HIF-1, as well as rheumatoid arthritis and cancer. Therefore, understanding the relationship between NF-B and HIF will greatly improve the development of drug development.
- HIF activity involves angiogenesis and also causes tumor growth, so inhibitors of HIF, such as Phenethyl isothiocyanate and acridine yellow, are being tested for anti-cancer effects.
Hypoxia-inducible factor neurology
- Studies have shown that the use of HIF prolyl hydroxylase inhibitors in mice enhances hippocampal memory and increases the performance of erythropoietin.