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- Table of Contents
Facts about Hypoxia-inducible factor 3-alpha.
Plays a role in the progression of the cardiorespiratory system (PubMed:18070924). .
Mouse | |
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Gene Name: | Hif3a |
Uniprot: | Q0VBL6 |
Entrez: | 53417 |
Belongs to: |
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No superfamily |
Basic-helix-loop-helix-PAS protein MOP7; BHLHE17; bHLHe17HIF-3A2; Class E basic helix-loop-helix protein 17; HIF-3A4; HIF-3-alpha; HIF3-alpha; hypoxia inducible factor 3, alpha subunit; hypoxia-inducible factor 3-alpha; hypoxia-inducible factor-3 alpha 4; Inhibitory PAS domain protein; IPASHIF3-alpha-1; Member of PAS protein 7; MOP7PAS domain-containing protein 7; PASD7HIF-3A
Mass (kDA):
73.044 kDA
Mouse | |
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Location: | 7|7 A2 |
Sequence: | 7; |
Isoform 3 is expressed in endothelial cells of vessels and capillaries in alveoli of the neonatal lung (at protein level) (PubMed:18070924). Expressed in lung, brain, heart and kidney (PubMed:9840812). Isoform 2 is expressed in heart and lung (PubMed:12119283). Isoform 2 is highly expressed in the epithelial cell layer of the cornea with lower expression in the layers of ganglion cells, inner nuclear cells, and rods and cones of the retina (PubMed:11734856). Isoform 2 is expressed in the cerebellum only in the Purkinje cell layer (PubMed:11734856).
There are several biological assays that use antibodies against HIF1A, both polyclonal and monoclonal. These antibodies react with HIF1A in animal samples, including human, mouse and rabbit. HIF1A plays an important role in embryonic and tumor angiogenesis as well as in the pathophysiology ischemic diseases.
The gene HIF3A encodes three isoforms: HIF-1a, HIF-2a, and HIF-3b. The three isoforms contain the same basic helix-loop-helix-PAS domains, and each is responsible for binding to DNA. The HIF-a protein also contains two transactivation domains and a DNA-binding domain, and two long-form isoforms.
The Hif3a/Ucp1 relation is shown in a thermogenesis-induced model and PCR analysis of genomic DNA. The lower panels depict adipose tissue depots with corresponding fat cells. The Hif3A isoforms gene transcription was measured as 2-DDCt transcript mRNA relative housekeeping genes such b-actin, 18S transcript mRNA.
Three CpG spots in intron 1, HIF3A, were associated with BMI according to a study that examined the association between BMI (Body Mass Index) and methylation. BMI was also associated with two SNPs that were associated with HIF3A methylation. This proves the importance of testing the relationship between HIF3A and BMI.
Hypoxia-inducible factor (HIF) is an ab dimer that regulates hundreds of hypoxia-inducible target genes. HIF3A human mRNA undergoes complex alternative splicing. The long version also has transactivation capability. For example, HIF-3a2 co-overexpression results in upregulation of 59 genes involving DNA replication, vascular endothelial growth factor receptor signaling, urogenital system development, and erythocyte homeostasis.
HIF3A not only regulates glucose metabolism but also regulates leptin levels and adipogenesis. HIF3A levels were also significantly higher in subjects who had a higher average adipose mass. However, the association is not significant in subjects with type 2, diabetes.
Boster Bio HIF3A is derived by the mRNA from the HIF3A protein. This protein is essential for the development of pulmonary hypertension and plays a critical role in the process of endothelial-to-mesenchymal transition. HIF activity in the lungs may be too high, which can lead pulmonary vascular remodeling.
During PH, medial remodeling and endothelial dysfunction of pulmonary arteries cause an increase in pulmonary pressure. Both HIFs and HIF2a play an important role in PH pathogenesis. Inhibiting HIF2a in PAH mice reduced several hemodynamic parameters related to PH development. HIF2a also regulates a variety of biological processes related to PH. HIF2a knockdown can inhibit multiple biological processes that are associated with PAH, such as angiogenesis (the formation of new blood vessels).
Recent research revealed that fourteen GO terms were related to PAH. Three of the GO gene sets were enriched with HIF2a-mediated genes. These results have great potential to identify the pulmonary vasculature remodelling gene sets in PAH patients. These results also suggest that HIF2a gene sets might be used as a biomarker in PAH.
Hypoxia-induced PH, the most common form, is the most common. HIF2a plays a critical role in both types. Individualized treatment is required for this heterogeneous condition of PH. This is why the Boster Bio HIF3A is a promising therapeutic target for PAH. This is why this assay is so unique.
Boster Bio HIF3A antibody targets hypoxia-inducible protein 1 (HIF1A). It inhibits the activity of glucoxylase-1. PX-478 targets HIF1A and blocks the pathway at multiple levels. It also prevents it being translated into an mRNA. This antibody also inhibits tumor growth and reduces angiogenic cells.
Recent research has shown that obesity and BMI are associated with DNA methylation of HIF3A. The data was obtained from whole blood from 479 people and 635 women. These results show the importance of whole-blood DNA methylation profiling in monitoring epigenetic changes within other human tissues. HIF3A expression was also negatively associated with methylation levels.
These results indicate that HIF3A gene expression is associated with insulin sensitivity (and glucose metabolism), which are both critical factors in the development and progression of GDM. HIFs play a role in the development diabetes. However, it remains to be determined if methylation plays a role in the development these metabolic disorders. Although it is possible that HIF3A's level of methylation may play a role regulating the development and progression of diabetes, further research is needed to confirm this possibility.
Boster Bio's Anti HiF-1A antibody detects HIF1A in a high-sensitive and specific way. It inhibits glucoxylase-1 activity and affects several levels of the pathway. It is also highly selective for HIF1A. It blocks tumor growth, and reduces angiogenic tissue. Boster Bio Anti-HIF-1A antibody was shown to block tumor growth as well as inhibit glucoxylase 1 activation.
Boster Bio has five milligrams BSA, and 0.05mg of Thimerosal in its anti-HIF3A anti-HIF3A antibodies. The antibody reacts with HIF3 (497-514aaa) DNA from rats and humans. The peptide used in the production of the antibody can be purchased separately. There are also antibodies to a particular length of HIF3A. This antibody is ideal to study cancer, rheumatoid, and other neurodegenerative disorders.
PX-478 acts as a potent small molecule antagonist of HIF-1a. Preclinical studies showed that it had significant antitumor activity against various solid tumors, but not in patients with non-small-cell lung cancer. PX-478 inhibited HIF-1a in lung cancer cell lines as well as in vivo in orthotopic mouse models.
The mechanism by which HIF3A regulates the metabolism of fat tissue has not been elucidated fully. However, it has been shown that hypoxia increases the transcription of HIF3A genes associated with all promoter regions. The hypoxic environment also upregulates the expression of all HIF3A transcripts associated with all promoter regions. Hypoxia can also increase HIF3A transcription levels in adipose.
PX-478's effects were evaluated in mice with NCIH441 lung cancer cell lines and NCIN417 lung carcinoma cells. The mice were treated with PX-478 20 mg/kg daily for five days. PX-478-treated mice had been killed by day 62. Representative stained tissue sections revealed that cancer-associated cells had been detected in the tissue. HIF-3A, which inhibits cancer growth, is an important target in cancer.
PX-478 is effective in PD positive patients. However the study population was made up of SD patients. The drug was well tolerated, and was associated with long-term SD. HIF-1a inhibition also supports the idea HIF-1a could be regulated through other active metabolites that melphalan. This supports its continued exploration as a therapeutic target.
PX-478 inhibited the hypoxia inducible protein (HIF-1a), in a phase I dose escalation trial. HIF-1a regulates cells responses to hypoxia. It also increases tumor growth, and angiogenesis. The drug, derived from melphalan and a nitrogen mustard moiety, inhibited the expression of HIF-1a in vivo.
The cell response to stress and hypoxia are mediated by antibodies to HIF1A. The proteins are also expressed in many tissues, human and non-human, including tumors, myocardial ischemia, wound healing, and myocardial infarction. HIF1a is able to increase the expression of genes related to cell survival and proliferation in these conditions. Boster Bio's HIF1A anti-mouse antibody has been used for biological assays. It is part of Picoband(tm). This antibody reacts well with both mouse and rat tissues and can also be used in IHC/WB applications.
The boster bio HIF1A antibody targets HIF1A and inhibits glucoxylase 1 activity. PX-478, an antibody that binds HIF1A to multiple levels, prevents acetylation and translation. It is a useful tool to detect high levels of HIF1A due to its selective nature. It also inhibits tumor development by reducing the angiogenic cells.
HIF1A protein must be expressed in high levels in biological assays. Intracellular oxygen tightly controls HIF1A levels in the body. Hypoxia does not affect HIF1A expression, unlike its counterpart. Hypoxia is used in tumor cells to maintain their metabolic and oxygen stability. Hypoxia promotes tumor growth and invasion. HIF1a is necessary for the development of embryonic cell and the growth tumors. However, HIF1a is often overexpressed in diseases like myocardial damage, carcinogenesis, and wound heal. HIF1A activates many proteins that are involved in the survival of cells within the inflammatory microenvironment.
Boster Bio HIF1A antibodies are highly sensitive to phosphorylated HIF1A. These antibodies target HIF1A, a central transcription element that plays an important role during embryonic vascularization (EV) and tumor angiogenesis. HIF1A activates more 40 genes in response hypoxia. HIF1A activation via NCOA1 or NCOA2 as well as the interaction between HIF1A/APEX promotes ubiquitination.
PMID: 9840812 by Gu Y.Z., et al. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3alpha.
PMID: 11734856 by Makino Y., et al. Inhibitory PAS domain protein is a negative regulator of hypoxia- inducible gene expression.