Study reveals additional, vital role for iron regulation proteins
The proteins that regulate the levels of iron in our body are also crucial for nutrient and water absorption in the gut, new research reveals. The study, which was partly funded by the EU, is published in the journal Cell Metabolism. Iron plays an important role in a number of processes in our bodies, and is also a central component of red blood cells. However, too much iron can be dangerous for our health. A large number of proteins, known as iron regulatory proteins (IRPs), work to ensure that our iron levels neither dip too low nor get too high. In this latest piece of research, scientists at the European Molecular Biology Laboratory (EMBL) and the German Cancer Research Centre studied two of these proteins, namely IRP1 and IRP2, in living mice. Studying the effects of these genes is not an easy task; if both genes are switched off throughout the body, the mouse dies before birth. If just one gene is switched off, the other gene compensates for this and few effects can be seen. To get around this problem, the scientists had to create a mouse in which both genes were switched off in the intestine only. 'We generated the first living organism lacking both IRPs in one of its organs,' explained Bruno Galy of the EMBL. To the scientists' surprise, the lack of IRPs in the guts of the mice did not lead to iron metabolism problems in the blood and tissues. However, the mice suffered from a number of other, unexpected problems. At two weeks of age, the test mice were half the size of their normal littermates, in spite of a normal food intake. They were also weaker and suffered from diarrhoea, showed signs of dehydration and eventually died at four weeks. 'These animals die before weaning, probably as a consequence of dehydration,' the researchers write in their article. 'Thus, IRPs are essential for intestinal function and organismal survival.' Investigations of the intestines of these mice revealed major problems with their structure and organisation, which the scientists believe affected the absorption processes in the intestinal cells. The study also shed new light on the role of the IRPs in the gut's iron metabolism. IRPs control the abundance of iron transporters in the membrane of intestinal cells. In the mice lacking IRPs, there were fewer iron importers in the membrane facing the gut, meaning less iron was absorbed from food passing through. In contrast, there were more iron exporters on the interface between the intestinal cells and the blood stream. In this way, the body's overall iron levels were kept stable but the iron stores of the intestinal cells themselves were depleted. The scientists believe this lack of iron in the intestinal cells could have been behind their structural problems. 'Since IRPs were discovered 20 years ago we have not been able to pin down what exactly they are doing,' said Matthias Hentze, Associate Director and group leader at EMBL. 'The new insights provided by our mouse model greatly advance our understanding of their function in iron metabolism and reveal that IRPs play a vital role for the survival of an organism.' The findings could be used to develop strategies to control iron absorption in the gut, and develop therapies for the treatment of iron overload disorders. EU support for the work came from the Euroiron1 project, which is funded under the 'Life sciences, genomics and biotechnology for health' priority of the Sixth Framework Programme (FP6).
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