Scientists discover key to surviving low oxygen levels
Lowering levels of an oxygen-sensing molecule can enable muscles to survive when oxygen is scarce, according to new research from an international team of scientists. The findings could lead to the development of new treatments for cardiovascular diseases and to improve the preservation of organs destined for transplantation. Humans, and indeed most multicellular organisms, rely on oxygen to convert fats and sugars into energy. Nevertheless, many animals are able to survive in environments where oxygen levels are extremely low. These include birds which fly at high altitudes, animals that live underground and animals that dive for long periods. Creatures which hibernate or undergo similar periods of dormancy have also developed strategies to conserve oxygen. Central to these strategies is a drastic reduction in oxygen consumption, often more than tenfold. 'Surprisingly little is known, however, about the molecular mechanisms underlying these adaptations,' the scientists write in their article, which is published online by the journal Nature Genetics. Led by researchers at the Flanders Institute for Biotechnology (VIB), the scientists studied the role of an oxygen-sensing molecule called Phd1. This molecule acts like an 'oxygen meter', and plays an important role in adapting the body's metabolism during the switch from an oxygen-rich to an oxygen-poor environment. The researchers created mice which were unable to produce Phd1 and then blocked an artery, thereby blocking the flow of oxygen to the muscle. To the scientists' surprise, this action did not lead to the death of the muscle, even though the muscle had received too little oxygen to survive under normal circumstances. Further investigations revealed that in the Phd1-deficient mice, the tissue had 'reprogrammed' itself to a metabolic state which uses less oxygen and so allowed the muscle to continue to function in a low oxygen environment. 'Our genetic study shows that Phd1, which acts as an oxygen sensor, controls this switch in skeletal muscle in vivo and, in doing so, determines hypoxia tolerance,' the scientists write. In another experiment, the researchers briefly treated healthy mice with a Phd1-blocker and achieved the same result. According to the scientists, the findings have implications for a number of medical applications. For example, in a heart attack, the heart muscle itself suffers from a lack of oxygen when the blood vessels which provide it with oxygen become blocked. Now, scientists can see whether using Phd1-blockers could protect hearts from the damage caused by a heart attack. Treatments could also be developed for strokes, and surgeons carrying out operations could safely cut the oxygen supply to organs for a longer time. The possible role of Phd1 in maintaining hibernation-like states leads the researchers to speculate that the molecule could also be used to 'hibernate' organs slated for transplantation. Currently, prolonged lack of oxygen is a major problem for doctors seeking to ensure organs remain viable.
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