生物谷報道：歐洲分子生物學實驗室（EMBL）的科研人員發(fā)現(xiàn)一種調(diào)節(jié)機體鐵離子含量的蛋白在營養(yǎng)和水吸收功能上發(fā)揮著重要的作用。如果缺少這種蛋白,，機體就會出現(xiàn)消瘦和脫水的癥狀,。這篇文章發(fā)表在細胞代謝雜志上。
鐵離子是紅細胞的一種重要組成部分,，在機體中發(fā)揮著許多重要的功能,。太多或太少的鐵離子都會影響身體健康,，因此身體中有一系列蛋白控制著鐵離子代謝過程,。EMBL實驗室的科研人員最終篩選出兩種最重要的蛋白,，鐵離子調(diào)節(jié)蛋白1和2（IRP1和IRP2）,。
生物谷專家表示,，鐵離子調(diào)節(jié)蛋白已經(jīng)發(fā)現(xiàn)了有20年之久，但我們卻很少了解這些蛋白所產(chǎn)生的功效,。其中IRP1被證實在不同的細胞中有兩種功能,，在富鐵細胞中的作用是催化，而在貧鐵細胞中,，它幫助調(diào)節(jié)涉及鐵輸運,、存貯、或利用的基因的表達,。如果能夠進一步的研究,，可以生產(chǎn)出因吸收障礙而導致的貧血。（生物谷：boysun2004編譯）
英文原文：
Proteins that regulate iron metabolism serve critical functions in nutrient and water absorption in the gut
Researchers from the European Molecular Biology Laboratory [EMBL] have discovered that proteins that regulate the body's iron household play a vital role in making sure enough nutrients and water are absorbed in the intestine. Mice lacking these proteins suffer from weight loss and dehydration, the scientists report in the current issue of Cell Metabolism.
Iron is a central component of red blood cells and has many other important functions throughout the body. Since too little or too much iron is dangerous for our health, a range of regulatory proteins tightly controls iron metabolism. EMBL scientists now assessed the role of two of these proteins, iron regulatory proteins 1 and 2 [IRPs], for the first time in living mice and found that their effects are much broader than previously assumed.
"We generated the first living organism lacking both IRPs in one of its organs," says Bruno Galy, who carried out the research in the lab of Matthias Hentze at EMBL. "This was extremely challenging, because if both proteins are switched off throughout the whole body, the mouse dies before birth. But if you switch off only one IRP, the one that is still intact substitutes and you can hardly see any effects."
Surprisingly, the lack of IRPs in the intestine did not upset the mice's iron household in blood and tissues. Instead the mice suffered from other, unexpected problems: they weighed only half of their normal littermates, suffered from severe dehydration and died only 4 weeks after birth. The general nutrient and water absorption in the gut was impaired. A closer look at the intestinal tissues revealed that their structure and organisation were completely disturbed, which likely affects all absorption processes that happen in intestinal cells. The findings show that IRPs are essential for intestinal function and the survival of an organism, but the details of how they accomplish their effects is unclear.
Although the global iron household was unaffected by the lack of intestinal IRPs, the scientists observed changes in the local handling of iron in the gut. IRPs control the abundance of iron transporters in the membrane of intestinal cells. Without the IRPs less iron importers are found in the membrane facing the gut, but iron exporters on the interface with the blood stream are increased. The results are less iron absorption, but more export of the metal into the bloodstream. In the short term this will keep the global iron content stable while depleting the iron stores of intestinal cells, which could be the reason for their disturbed structure and tissue organisation.
"Since IRPs were discovered 20 years ago we have not been able to pin down what exactly they are doing," says 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 might help inform the development of strategies to control iron absorption in the intestine, which might pave the way for alternative therapeutic approaches to treat iron overload disorders such as hemochromatosis.
