This discovery, funded by the National Space Biomedical Research Institute (NSBRI) and the Muscular Dystrophy Association, increases the understanding of how muscles atrophy and may lead to development of new treatments for muscle wasting on Earth and in space.
"Through a study of rat muscles, we determined that atrogin-1 is found only in muscle," said Dr. Alfred Goldberg, professor of cell biology at Harvard Medical School and associate leader of NSBRI's team of scientists focusing on muscle loss in space. "In normal muscles, the amount is low; however, there is a dramatic increase in the production of the atrogin-1 protein in conditions where muscles lose size and strength."
In healthy muscles, there is a continual process of muscle protein production and breakdown. With muscle-wasting conditions, this cycle gets out of balance. Protein breakdown occurs more rapidly than protein production, leading to loss of muscle weight.
"Proteins in cells are destroyed in a structure called the proteasome," Goldberg said. "From clues in its gene sequence, we guessed that atrogin-1 was a component of this pathway of protein breakdown and succeeded in proving atrogin-1 targets other proteins for destruction."
Goldberg and associates, Dr. Marcelo Gomes, Dr. Stewart Lecker and Dr. Thomas Jagoe, set out to look for genes activated only during muscle atrophy. Using gene microarray analysis, the group studied muscle samples from healthy rats and those experiencing various muscle-wasting conditions.
"Genes code for the various proteins in our cells, and the information in our genes is expressed through the use of molecular messengers, called messenger RNAs," Goldberg said. His group searched atrophyin
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Contact: Kathy Major
major@bcm.tmc.edu
713-798-5893
National Space Biomedical Research Institute
20-Mar-2002