New insight into oxygen deprivation
10 March 2009
The way fish survive in waters with little oxygen may lead to a new understanding of oxygen deprivation in patients on intensive care units, according to new research.
A model of the protein Myoglobin. The protein - one of the most-studied proteins of all time - stores oxygen in muscle tissues.
UK researchers investigating one of the most-studied proteins of all time, myoglobin, were surprised to find it appearing in unexpected places in common carp and zebrafish when oxygen levels plummeted.
Myoglobin receives oxygen from haemoglobin - the protein that carries oxygen in red blood cells - and stores it in muscle tissues, notably the heart, until needed.
But researchers led by Professors Andrew Cossins and Anja Kipar from the University of Liverpool have, for the first time, found myoglobin in many other, non-muscle, tissues like kidneys, livers, gills and brains.
Diving mammals like whales need large amounts of myoglobin to store oxygen in their muscles during long dives.
The new work, published in the Journal of Experimental Biology shows that the amount of myoglobin increased markedly - doubling or even quadrupling - following five days of living in water with little oxygen.
They also show that the protein was concentrated in the cells lining blood capillaries, indicating a new function
The team believe this shows that myoglobin may serve a previously-unknown purpose in these tissues: helping the organs survive low oxygen environments. What's more, this newly-discovered function is likely to be the same in all vertebrates, including mammals.
'Profound' implications
Cossins says, 'From a biomedical viewpoint, the implications are profound, because it could relate to any cardiovascular pathology such as stroke or infarct [dead tissue caused by loss of blood supply].'
The researchers analysed 13,000 carp genes.
A possible explanation for myoglobin in cells lining capillaries is that during oxygen deprivation - or hypoxia - the protein may make nitric oxide causing capillaries to dilate. As capillaries expand, blood flow to the organs will quicken, minimising cell death caused by oxygen starvation.
Sir John Kendrew first described the structure of the myoglobin protein, earning him the 1962 Nobel Prize in chemistry.
Biologists have long accepted that the only use of myoglobin, which gives meat its red colour, is as an oxygen store in heart and muscle cells. It ensures muscles always have enough oxygen even during exertion.
Diving mammals, such as whales, seals and dolphins, wouldn't be able to hold their breath during long dives without high quantities of the protein storing oxygen in their muscles. In fact whale muscle contains so much of the protein that whale meat is black. Similarly, myglobin levels in mountain climbers' hearts and other muscles increase at high altitudes.
13,000 carp genes analysed
The project, funded by the Natural Environment Research Council, began as a study of stress tolerance mechanisms in fish. The group made the discovery while systematically studying how stress affected 13,000 carp genes. They were looking for unexpected signals.
'I was interested in how fish coped with seasonal stresses like heat and cold, and hypoxia, because these are a common problems in freshwater habitats' recalls Cossins.
'We came up with dozens of genes with interesting responses and these became new candidates for study', says Cossins. The research team looked at several types of tissue in fish that were coping with cold exposure and hypoxia, and to their surprise found a myoglobin signal in the liver, a tissue where myoglobin had never before been found.
'Carp is perfect for this work because it routinely puts up with seasonal cold and daily hypoxia, and it can cope; but the question is, how?'
'This is something we discovered by looking at an animal with a very specialised way of life, that we would never have discovered just by looking at a mouse or a human. You sometimes have to find extreme forms to see how unusual something is,' says Cossins.
Insights into how zebrafish and carp survive in low-oxygen habitats could be used to help patients in intensive care units.'
The question Cossins and his colleagues are now trying to answer is whether other vertebrate animals express genes for myoglobin production beyond hearts and muscles. Preliminary evidence suggests they do.
Hypoxia is a condition that affects almost all intensive care patients on ventilators to some degree, and can lead to heart attack and stroke.
Heart attack and stroke are the two most common causes of death in the UK, with one person dying from a heart attack every six minutes. The discovery could help pave the way for medical treatments targeting myoglobin as a way to help patients suffering oxygen deprivation on intensive care wards.
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