Research Profiles
The proteomics of weightlessness
the microgravity effects,” he explains. More proteins were decreased in abunSpaceflight looks like fun. We’ve all dance in suspended mice compared seen television footage of astronauts with control mice; this finding also gently floating through their spacecraft, agrees with results from previous studunencumbered by gravity. But exposure ies, he adds. to weightlessness can wreak havoc on The researchers also validated the human physiology. Because astronauts levels of b-synuclein and pyruvate dedo not experience the force of gravihydrogenase, which were both downty for several days or months during regulated in suspended mice, by westspace missions, muscles atrophy ern blotting. Ramesh says that and bone is lost. Fluid rushes to synuclein protects brain cells from apoptotic events, so m icrogravity the head and upper body during spaceflight; this causes a buildup could hasten cell death. Pyruvate of pressure in the brain. In space, dehydrogenase is involved in carthe heart does not have to work bohydrate metabolism and was as hard to pump blood throughexpected to decrease because meout the body; this can cause probtabolism is reduced in humans lems when the astronauts return who travel in space. to Earth and again experience the Studies are already under way in full force of gravity. the researchers’ laboratories to exAs described in this issue of JPR amine other brain regions, such (pp 548–553), Govindarajan Raas the hypothalamus and fronmesh, Shubhashish Sarkar, and tal cortex, in suspended mice by co-workers at Texas Southern proteomics methods. One of RaUniversity, the University of Texmesh’s specific goals is to develpI 10 (b) MW 3 as, the University of Alabama at op countermeasures for the effects (kDa) they have observed. In previous Birmingham, and the U.S. Na150 tional Aeronautics and Space studies, his group has shown that 75 Administration–Johnson Space oxidative stress occurs in the 50 1 Flight Center used proteomics brain tissue of suspended mice, 17 8 techniques to study the molecular so he plans to administer antiox5 25 18 effects of weightlessness, or miidants to the suspended mice to 20 crogravity. They found that sevsee whether the protein levels re25 15 14 12 13 21 eral proteins in the hippocampus turn to normal. Sarkar says that he 10 were differentially regulated in would like to obtain space-flown rodent tissue to compare with the mice exposed to a simulated miAre we in space yet? (a) In the tail-suspension model, a crogravity environment. data generated in this proteomics caged mouse is elevated at an angle of ~20° to simulate Because of the financial and study. In addition, he will test the effects of microgravity. (b) Representative 2DE gel technical difficulties of sending whether the protein changes in from mice that spent 7 days in a simulated microgravity research animals into space, the simulated microgravity are reversenvironment. Proteins that were differentially expressed scientists wanted to perform their ible. “We plan to suspend the mice, are indicated with arrows. experiments on the ground. But keep them in this microgravity environment for 7 days, and then how do you study microgravity on Earth? According to Ramesh, a widegels. In total, 25 spots were quantitawe’ll take out the mice and rest them ly accepted method for in vivo mouse tively different between the 2 groups for 2 days, 4 days, 6 days, or a month,” studies is the tail-suspension modof mice. The researchers identified the he says. “If it causes a permanent effect, el. A partially unbent paper clip is atproteins in 11 of the spots that differed then that means something is going on tached to the tail of a mouse by a molethe most; 7 were down-regulated and 4 in the genome, and then we [will have skin strip that is wound around the tail were up-regulated in suspended mice. to] look at the genome.” and clip. The other end of the paper clip Several structural and metabolic proAccording to Ramesh, this study has is hooked onto a swivel pulley connectteins were identified. Tubulin, a strucblazed a trail for researchers analyzed to a bar at the top of the cage. “This tural protein, was down-regulated in ing the physiological effects of being mouse can move in the cage like a normice after exposure to simulated miin space. “I think this paper will realmal mouse; it can drink, it can eat food, crogravity. Sarkar says that other rely open the eyes of a lot of [scientists] and it can move in a full 360º range of searchers have also observed modified working on microgravity-related work,” motion,” says Ramesh. He adds that the structural proteins in animals exposed he says. “Ultimately, everything comes model is a good approximation for mito microgravity environments. “We got [down] to protein levels. I think protein crogravity because the researchers obthis [result too], so we know our modis the key.” serve changes in fluid distribution, el is somehow able to touch on some of —Katie Cottingham GOVINDARAJAN RAMESH
bone strength, calcium levels, and immune function in the suspended mice that are similar to those that occur in astronauts. Brain tissue from control mice was compared with tissue from mice that spent 7 days in the simulated microgravity environment. The hippocampus regions were removed, and the proteins were extracted and run on 2DE
468 Journal of Proteome Research • Vol. 5, No. 3, 2006
