Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists discover protein that allows safe recycling of iron from old red blood cells

06.02.2013
Offers promise of new treatments for iron deficiency and parasitic worm infections

Humans survive by constantly recycling iron, a metal that is an essential component of red blood cells, but which is toxic outside of those cells. More than 90 percent of the iron in an adult human's 25 trillion life-sustaining red blood cells is recycled from worn-out cells.

Almost 50 years ago scientists first began hypothesizing that our bodies must have a special protein 'container' to safely transport heme -- the form of iron found in living things – during the breakdown and recycling of old red blood cells and other types of heme metabolism. Now a team of scientists from the University of Maryland, Harvard Medical School, the National Institutes of Health and the University of Utah School of Medicine have identified this long-sought heme-iron transporter and shown that it is the same HRG1 protein that a common microscopic worm, C. elegans, uses to transport heme. In humans, the iron in heme is the component that allows hemoglobin in red blood cells to carry the oxygen needed for life.

The team's findings are based on studies in human, mouse, zebrafish and yeast systems and are published in the Feb. 5, issue of the journal Cell Metabolism.

"Our current work reveals that the long-sought heme transporter that permits humans to recycle over 5 million red blood cells per second in our spleen and liver, is the same HRG1 transporter protein that my students and I discovered in worms in 2008, and which we showed at that time is used by C. elegans to safely carry heme-iron that it obtains from dirt into its intestine," says team leader and corresponding author Iqbal Hamza., a University of Maryland associate professor in the Department of Animal & Avian Sciences.

"Moreover, we show in this current study that mutations in the gene for HRG1 can be a causative agent for genetic disorders of iron metabolism in humans," he says.

First author Carine White, a UMD post-doctoral researcher and three other students from his lab joined Hamza in the research, along with researchers from Harvard, NIH and Utah.

This study's findings are the third major piece that Hamza and his Maryland lab have added to the puzzle of understanding how humans and other organisms safely move heme around in the body. In addition to their two studies showing the role of the HRG1, that Hamza showed in a 2011 Cell paper that in C. elegans there is a different, but related, protein called HRG3 that transports heme from the mother worm's intestine to her developing embryos.

According to Hamza, the HRG3-mediated pathway that worms use for transporting heme to developing oocytes also appears to be an excellent target for stopping the reproduction of hookworms and other parasites that feed on host red blood cell hemoglobin. Together these three findings could lead to new methods for treating two age-old scourges - parasitic worm infections, which affect more than a quarter of the world's population, and problems of iron metabolism and iron deficiency. The latter is the world's number one nutritional disorder. With the help of UMD's Office of Technology Commercialization and the university's Maryland Technology Enterprise Institute, Hamza has started a company, Rakta Therapeutics, Inc. that focuses on developing anti-parasitic drugs that specifically target the parasite's variation of HRG1 and HRG3 transporters.

Heme, Humans and Bloodless worms

In living organisms -- ranging from humans to baker's yeast -- iron enclosed in a heme cage is a critical molecule for health because it binds to oxygen and other gases needed for survival. However, because heme is toxic, scientists long ago started searching for the existence of proteins that could safely transport heme between cells and throughout the body.

However, identifying such proteins has been a very difficult task because organisms generate heme in a complicated eight-step process that is hard to control for in studies of heme transport pathways.

Hamza first started trying to uncover the secrets of heme transport in 2003. After briefly and unsuccessfully studying the question of heme carrying proteins in traditional bacteria and mice models, Hamza switched to a non-intuitive study subject, one that doesn't make heme, but needs it to survive, that doesn't even have blood, but shares a number of genes with humans - the C. elegans roundworm. C. elegans gets heme by eating bacteria in the soil where it lives. "C. elegans consumes heme and transports it into the intestine.

According to Hamza, C. elegans has had several other benefits for studying heme transport. Hamza's team had control of the amount of heme the worms were eating. With only one valve controlling the heme transport, the scientists knew exactly where heme was entering the worm's intestine, where, as in humans, it is absorbed.

Moreover, C. elegans is transparent, so that under the microscope researchers could see the movement of the heme ingested by a live animal.

"HRG1 Is Essential for Heme Transport from the Phagolysosome of Macrophages during Erythrophagocytosis," Cell Metabolism, Feb. 5, 2013.

Scientist Contact: Iqbal Hamza, Ph.D., Associate Professor, University of Maryland, College Park; Phone: 301-405-0649; Email: hamza@umd.edu

Lee Tune | EurekAlert!
Further information:
http://www.umd.edu

More articles from Life Sciences:

nachricht Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory

nachricht How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>