Jueves, 22 Junio, 2017

When oxygen is scarce, naked mole-rats metabolize fructose like plants

Even tougher than we thought Even tougher than we thought Roland Gockel MDC
Danilo Martir | 20 Abril, 2017, 23:53

They found that naked mole-rats can survive conditions that would kill other mammals - including humans - within minutes. After 5 hours, we realized that five percent oxygen was not a problem for these guys so we decided to make 5 hours our limit. We had no idea how the naked mole-rat would respond, so we were ready to abort the experiment if things looked bad. The rodents are freaky in just about every way. Also, they reduce their need for oxygen by not generating body heat-they are the only cold-blooded mammal.

An global team of scientists led by Thomas Park, from the University of IL at Chicago, has discovered the biological mechanism employed by naked mole-rats to live without oxygen. But even after 18 minutes in the chamber, they recovered completely when exposed to normal air, the researchers write today in Science.

Within a minute or so, mice and other mammals pass the point of no return. By doing so, they are able to generate energy anaerobically, placing themselves into a "suspended animation-like state". It has been known for some time that the hemoglobin in their blood is very sticky for oxygen, able to grab oxygen molecules out of atmospheres with very low oxygen levels. With all those rodents breathing and clogging up burrows, they often encounter low-oxygen and high-carbon dioxide conditions. "I can understand why people think so, because they're so unusual looking, but if you get to know them, they're actually very gentle, they're friendly creatures". Now, scientists have discovered another superpower: The animals can survive more than 18 minutes without oxygen.

They watched closely, ready to pull the mole-rats out at the first sign of trouble.

"To me, that's something that makes them very lovable", Park said. But now U.S. and German researchers have even more fantastic news for us.

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The animals had slowed down a bit, he says, but were awake, walking around and even socializing.

"They live in really challenging conditions", says Chris Faulkes of Queen Mary, University of London, who studies mole rats, but wasn't involved in the research. After five hours at five percent oxygen, the team chose to take the subjects out of their test chamber because nothing was happening.

"And that was a surprise, too", he says. Mice without oxygen die after around 20 seconds.

According to Park and colleagues across three continents, the rodents do have a trick up their sleeves. "The downside in glucose is that it requires the use of oxygen, so when you take oxygen away, the glucose pathway is kind of screwed". Within one or two minutes, energy-carrying molecules like ATP are used up and brain cells start to die.

In low-oxygen conditions, they enter a coma-like state and release fructose into the blood. When naked mole-rats are oxygen-deprived, a unique metabolic pathway throws the species' cells a lifeline. Our cells have to convert it into glucose in order to use it. Energy stores are quickly depleted, especially in the brain, and cells start dying.

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"They have a social structure like insects, they're cold-blooded like reptiles, and now we found that they use fructose like a plant", Park says.

North American freshwater turtles and goldfish, for example, spend their winters in oxygen-lacking, ice-covered lakes and ponds. On the other hand, naked mole-rats live in an oxygen poor environment.

RG: How do they use fructose? .

"Together this allows the naked mole rat to use fructose as fuel instead of glucose when there is no oxygen", Lewin says. If we could activate the fructose pathway, we could significantly extend that time window.

Storz imagines mole-rats aren't the only extreme animals with potential clues to alleviating human medical problems.

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"There's a lot of negative issues (in humans) that come from consuming fructose, and my feeling is that the naked mole rat has figured out how to beat those negative side effects", said neurobiologist and UIC professor Thomas Park who led the global team of researchers.

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