Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

After a 40-year search, a hormone controlling iron metabolism in mammals is finally identified

04.04.2002


Iron is vital for cells, because it catalyzes key enzyme reactions; it is also crucial for respiration, fixing atmospheric oxygen to hemoglobin in red blood cells. Iron deficiency can lead to severe anemia, with inadequate tissue oxygenation. An excess of iron is also toxic, as it facilitates the generation of free radicals that can attack the liver, heart and pancreas. This is the case in hereditary hemochromatosis, a genetic disorder which, in 80% of cases, is linked to a point mutation in the Hfe-1 gene, leading to excessive iron uptake by the intestinal tract. Hereditary hemochromatosis is very frequent in western countries, affecting one in 300 people. The body has no physiological mechanism for eliminating iron, and the only effective treatment for patients with hereditary hemochromatosis is bleeding, in some cases several times a week. These patients, and their doctors, are eagerly awaiting a breakthrough in our understanding of the mechanisms regulating iron metabolism, that might have therapeutic implications.



Dietary iron enters the body via cells known as enterocytes, that line the intestinal folds. Humoral signals are known to modulate how much iron these cells take up, according to the body`s internal stores. Yet, despite intense research over the last four decades, no-one had previously been able to identify these signals.

It is by chance that Gaël Nicolas, Sophie Vaulont and their coworkers came across such a signal while working on knock-out mice developed in their laboratory. The mice lacked a transcription factor known as USF2 (upstream stimulatory factor 2), thought to be involved in glucose metabolism. To their surprise, the team found that the mice had disorders similar to those of patients with hereditary hemochromatosis, namely premature ageing of the pancreas and liver, which take on an abnormal brown color - a sign of iron accumulation. Further tests indeed showed that the animals had a form of hemochromatosis. Intrigued, the team created a subtractive RNA bank in order to determine whether any other genes were abnormally expressed in their model. This was effectively the case. One abnormally expressed gene was found to correspond to a recently identified sequence of 25 amino acids found in members of an antimicrobial peptide family called the defensins. The peptide in question - hepcidin - is produced by the liver and secreted into the bloodstream. Hepcidin has a degree of antimicrobial activity, but Axel Kahn, Sophie Vaulont and their colleagues at Bichat Hospital in Paris believe that it acts essentially as a true hormone, inhibiting iron uptake by intestinal cells; they also believe that when hepcidin dysfunctions the body has no way of limiting iron absorption into the bloodstream.


To test this hypothesis, the team first checked that iron levels were normal in a transgenic mouse model, produced in another laboratory, that lacks USF2 but has an intact hepcidin gene. Then they went on to create transgenic mice whose livers overproduced hepcidin, expecting them to develop anemia. In the event, almost all the new-born animals were smaller than normal, had very pale skin and no hair, were profoundly anemic, and died within hours of birth - unless they received an injection of iron. (Some animals producing less hepcidin were less severely anemic and survived without treatment.)

This discovery opens up exciting therapeutic and diagnostic perspectives in diseases due to abnormal iron homeostasis. Therefore, a patent application has been filed by INSERM and the inventors. One short-term possibility is a diagnostic test based on serum hepcidin measurement. In the longer term, the development of hepcidin agonists and antagonists may well transform the treatment of these frequent and potentially severe disorders.

Nathalie Christophe | alphagalileo

More articles from Life Sciences:

nachricht Designer cells: artificial enzyme can activate a gene switch
22.05.2018 | Universität Basel

nachricht Flow of cerebrospinal fluid regulates neural stem cell division
22.05.2018 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Designer cells: artificial enzyme can activate a gene switch

22.05.2018 | Life Sciences

PR of MCC: Carbon removal from atmosphere unavoidable for 1.5 degree target

22.05.2018 | Earth Sciences

Achema 2018: New camera system monitors distillation and helps save energy

22.05.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>