The findings, which are reported this week in the online publication of The Journal of Clinical Investigation, represent a collaborative effort between the laboratories of Randall Johnson, Ph.D., UCSD professor of biology and Victor Nizet, M.D., professor of pediatrics and pharmacy at the UCSD School of Medicine and Skaggs School of Pharmacy and Pharmaceutical Sciences.
Iron is essential for many normal biological processes including the production red blood cells that deliver oxygen to the body's tissues. By studying the regulation of iron and production of red blood cells in mice, the researchers established the relationship between a pair of proteins that play a central role in monitoring a hormone called hepcidin.
The hepcidin hormone is a peptide, or small protein, that is synthesized in the liver and regulates the levels of iron in the body. It prevents the body from absorbing more iron than is needed from food or supplements, and blocks the export of iron from cells.
Patients with cancer, chronic inflammatory diseases or infections often develop high levels of hepcidin, which reduces the amount of iron available to support the production of new red blood cells. Consequently, such patients suffer from low red blood cell production, or anemia.
To properly respond to anemia, the body must somehow reduce hepcidin in order to increase the iron that is needed for red blood cell production. Until now, scientists didn't clearly understand the mechanisms by which hepcidin itself is regulated.
The UCSD research team discovered that a protein known as hypoxia-inducible transcription factor (HIF) is critical in orchestrating the proper hepcidin response in the liver. In turn, HIF levels are controlled on a minute-by-minute basis by the action of another protein known as von-Hippel Lindau factor (vHL.)
“The vHL factor works to lower HIF levels whenever oxygen is high or iron is abundant,” said Johnson. “When iron levels and oxygen delivery to the tissues drop, as is the case in anemia, vHL ceases its action and HIF is preserved.”
Previous research had shown that HIF is responsible for stimulating erythropoietin (EPO), a hormone that instructs the bone marrow to produce new red blood cells. The UCSD team made the critical and novel observation that HIF also strongly inhibits the production of hepcidin in the liver.
“Our findings show that the vHL and HIF proteins play a central role in sensing and regulating iron levels,” said lead author Carole Peyssonnaux, Ph.D., a former researcher with Nizet and Johnson who has now joined the faculty of the Institut Cochin in Paris, France. “In anemia, the body responds to low iron and oxygen levels by increasing HIF, which in turn suppresses hepcidin and boosts EPO to provide the iron and new red blood cells required to correct the problem.”
Importantly, the researchers found that HIF was capable of suppressing hepcidin even in mice suffering inflammatory changes in their bodies.
“This key finding suggests that new drug treatment strategies to boost HIF or inhibit vHL could reverse the abnormally high hepcidin levels seen in the anemia that affects the majority of patients suffering from chronic infections or inflammatory disease,” said Nizet.
Debra Kain | EurekAlert!
A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich
New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
20.02.2017 | Materials Sciences
20.02.2017 | Health and Medicine
20.02.2017 | Health and Medicine