The function of hypoxia-inducible factor
On October 7, 17, the Swedish karolinska medical school announced in Stockholm that the Nobel Prize in physiology or medicine in 2019 will be awarded to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza, for their revolutionary to find let people understand the cells at the molecular level experience the basic principle of oxygen,They mainly studied the mechanism of hif level regulation by hypoxia-inducing factor.So what role does hif play?
1.Hif can activate PKM2 gene for transcription
PKM2 can alter glucose metabolism in cancer cells to participate in tumorigenesis, and PKM2 gene transcription can be activated by hypoxia-inducing factor 1 (hif-1).PKM2 interacts directly with the hif-1 alpha subunit and promotes trans-activation of the hif-1 target gene by enhancing the binding of hif-1 to anoxic responsive molecules and the recruitment of p300 to anoxic responsive molecules.The binding of PKM2 to hif-1 a and the co-activation of PKM2 were enhanced by the interaction between PKM2 and prolyl hydroxylase 3 (PHD3). The hydroxylation of PKM2 to prol-403/408 was confirmed by mass spectrometry and anti-hydroxyproline antibody assay.PHD3 knockout can inhibit the co-activation function of PKM2, reduce sugar intake and lactic acid production, and increase the oxygen consumption of cancer cells.Thus, PKM2 can participate in a positive feedback loop that promotes the trans-activation of hif-1 in cancer cells and reprogram their glucose metabolism.
2. Role in insulin resistance and the development of type 2 diabetes
Researchers at the university of Texas at Dallas found that the protein hif-1 alpha played a key role in the development of insulin resistance and type 2 diabetes in obese mice.The researchers used genetic engineering to make mice lose the protein hif-1 alpha in their fat cells.Hif-1 alpha was still produced in other cell types and tissues in the mice.Although the mice became obese when fed a high-fat diet, they did not develop insulin resistance and diabetes as the genetically normal obese mice did.The researchers say that developing hif-1 alpha inhibitors to block the protein's function could one day lead to new drug treatments for type 2 diabetes and insulin resistance in obese people.
3. Induction of lactic acid
In a hypoxic response process that relies on lactic acid accumulation, synthesis of lactic acid is increased under hypoxic conditions.NDRG3 is a newly discovered oxyregulatory protein that degrades via the PHD2/ vhl-dependent pathway at normal oxygen concentrations, but is able to avoid degradation by combining with accumulated lactic acid under hypoxic conditions.This stable NDRG3 binds to c-raf, mediates hypoxic-induced activation of the raf-erk pathway, and promotes angiogenesis and cell growth.Inhibition of intracellular lactic acid synthesis eliminates the hypoxic response mediated by NDRG3.This study reveals the molecular basis of the lactate-induced hypoxic response process and is of great significance for the development of targeted therapies for hypoxic-induced diseases.
If you are interested in ELISA Kits about HIF-1, welcome to visit our website:
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-Hu.pdf
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-Mu.pdf
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-p.pdf
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-Ra.pdf
1.Hif can activate PKM2 gene for transcription
PKM2 can alter glucose metabolism in cancer cells to participate in tumorigenesis, and PKM2 gene transcription can be activated by hypoxia-inducing factor 1 (hif-1).PKM2 interacts directly with the hif-1 alpha subunit and promotes trans-activation of the hif-1 target gene by enhancing the binding of hif-1 to anoxic responsive molecules and the recruitment of p300 to anoxic responsive molecules.The binding of PKM2 to hif-1 a and the co-activation of PKM2 were enhanced by the interaction between PKM2 and prolyl hydroxylase 3 (PHD3). The hydroxylation of PKM2 to prol-403/408 was confirmed by mass spectrometry and anti-hydroxyproline antibody assay.PHD3 knockout can inhibit the co-activation function of PKM2, reduce sugar intake and lactic acid production, and increase the oxygen consumption of cancer cells.Thus, PKM2 can participate in a positive feedback loop that promotes the trans-activation of hif-1 in cancer cells and reprogram their glucose metabolism.
2. Role in insulin resistance and the development of type 2 diabetes
Researchers at the university of Texas at Dallas found that the protein hif-1 alpha played a key role in the development of insulin resistance and type 2 diabetes in obese mice.The researchers used genetic engineering to make mice lose the protein hif-1 alpha in their fat cells.Hif-1 alpha was still produced in other cell types and tissues in the mice.Although the mice became obese when fed a high-fat diet, they did not develop insulin resistance and diabetes as the genetically normal obese mice did.The researchers say that developing hif-1 alpha inhibitors to block the protein's function could one day lead to new drug treatments for type 2 diabetes and insulin resistance in obese people.
3. Induction of lactic acid
In a hypoxic response process that relies on lactic acid accumulation, synthesis of lactic acid is increased under hypoxic conditions.NDRG3 is a newly discovered oxyregulatory protein that degrades via the PHD2/ vhl-dependent pathway at normal oxygen concentrations, but is able to avoid degradation by combining with accumulated lactic acid under hypoxic conditions.This stable NDRG3 binds to c-raf, mediates hypoxic-induced activation of the raf-erk pathway, and promotes angiogenesis and cell growth.Inhibition of intracellular lactic acid synthesis eliminates the hypoxic response mediated by NDRG3.This study reveals the molecular basis of the lactate-induced hypoxic response process and is of great significance for the development of targeted therapies for hypoxic-induced diseases.
If you are interested in ELISA Kits about HIF-1, welcome to visit our website:
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-Hu.pdf
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-Mu.pdf
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-p.pdf
https://www.dldevelop.com/uploadfile/data/DL-HIF1a-Ra.pdf
