Proteins are lost in space

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  • Published: May 15, 2006
  • Author: Steve Down
  • Channels: Proteomics
thumbnail image: Proteins are lost in space

There are those who see gravity as a hindrance, tying us to the surface of the Earth and limiting upward movement to a few feet at best. Put is into orbit around our planet in a spacecraft and we experience the full delights of weightlessness. Nothing is out of reach and we can float around the craft at our ease. Even catching our food in mid-air makes mealtimes more exciting.

However, humans have evolved in the permanent presence of gravity and our bodies rely on it to maintain correct functions. Take gravity away and strange things begin to happen. Since spaceflight began, it has been discovered that weightlessness reduces bone mass and muscle tissue in astronauts. Blood is no longer encumbered by gravity and rushes to the upper body, increasing the pressure in the brain. Studies on frogs, mice and rats sent into orbit have revealed a variety of physiological effects, including the modified production of peptides in the brain and the altered expression of genes.

These findings have a strong bearing on manned spaceflight. The effects occurred over relatively short flight times of a few days to a few weeks, so what will happen to humans on long space flights, such as those planned to Mars, or beyond? The answers do not come easily, bearing in mind the difficulty and expense of setting up experiments in space, even using the International Space Station.

Now, researchers in the US have provided an earthly solution by studying mice in a simulated microgravity environment. They used the well-established tail suspension model, in which the mouse was maintained at an angle of about 20°C to horizontal by permanently tying its tail to a swivel pulley attached to the top of its cage. Each mouse had as full movement as an unbound mouse, but raising the tail caused the body fluids to gravitate to the upper body as occurs under microgravity.

In previous work, the researchers, led by Govindarajan Ramesh from the Texas Southern University, had found that simulated microgravity induced oxidative stress, increasing lipid peroxidation in the hippocampal region of the male mouse brain. This encouraged them to study the effects on the proteome of the hippocampus, by comparing the proteins to those from control mice which had not been tail-suspended. After 7 days of suspension, the mice were sacrificed and proteins in the hippocampus were extracted, separated by 2D gel electrophoresis and identified by MALDI mass spectrometry.

A total of 11 differentially regulated proteins were analysed, seven being down-regulated and four up-regulated. The down-regulated proteins consisted of structural and metabolic proteins, indicating that structural proteins and metabolic activity are adjusted within the body to account for the altered environment. Other published work had also reported modifications in the structural proteins of animals in microgravity. This confirms the applicability of the tail-suspension model, said Ramesh.

Two of the affected structural proteins were tubulin and myosin, from the cytoskeletal group of proteins. Their reduced abundances imply that there may be loss of cellular structure during extended periods of weightlessness in space. One reduced metabolic protein was pyruvate hydrogenase, which is involved in carbohydrate metabolism. It was expected that this protein would be less abundant, since the human metabolism is reduced during space travel.

Another down-regulated metabolic protein was beta-synuclein, which prevents abnormal protein aggregation and protects the brain cells from apoptosis. Its reduced abundance suggests that microgravity could accelerate cell death due to the reduced protection.

Overall, the results imply that extended space travel could have serious effects on protein expression, although the mechanisms behind the changes and the full consequences are not yet understood.

Future work by the research team will focus on different areas of the brain and will attempt to see if these changes are reversible, by releasing the mice from the tail-suspension device and letting them survive normally for a period of time before brain analysis.

International Space Station
Long stays on the International Space Station may affect the proteins in the brain  

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