Researchers learn how degradation of proteins changes muscles during exercise

DALLAS - March 17, 2000 - Sedentary white rabbits have given UT Southwestern Medical Center at Dallas researchers a glimpse of the molecular changes that alter the structure and function of muscles following exercise training. This knowledge may lead to drugs that would benefit people with muscle-degenerative diseases or sports injuries.

The study, published in the March Journal of Applied Physiology, demonstrates how a pathway controls the breakdown of specific proteins that regulate whether a muscle will provide endurance for activities such as long-distance running or cycling or will provide speed and strength for sprinting or weightlifting.

The biochemical system, called the ubiquitin/proteasome pathway, determines which proteins within a muscle cell undergo degradation thus allowing the switching of muscle type. The protein ubiquitin tells the cylinder-shaped catalytic enzyme, the proteasome, which proteins to degrade.

"We hypothesized that protein degradation, and specifically this protein degradation pathway, plays a role in this change," said Dr. George Ordway, associate professor of physiology. "The study shows the potential role the pathway plays in the remodeling of fast-twitch glycolytic, fatigable strength muscle into slow-twitch, oxidative, fatigue-endurance muscle that occurs normally in exercise training or anytime the muscles are constantly contracted."

Because the laboratory rabbits are normally sedentary, when a selected fast-twitch muscle was stimulated to contract continuously, it was relatively easy for scientists to monitor the biochemical associated with its change to a slow-twitch muscle. The investigators found an increase both in the level of the proteasome and in its activity in the active rabbits' muscles. Concurrently, many of the proteins characteristic of the fast-twitch glycolytic muscle were eliminated.

The scientists already know that the remodeling involves changes in many different proteins. Now they are studying exactly which proteins the pathway degrades. They also want to determine if changes in muscle types are altered by age, types of exercise, diet or a combination of these factors and how fast the muscle remodeling occurs.

"What we have seen so far is just for the whole muscle," Ordway said. "Now we are looking at sections of muscle to find out if these changes are fiber-type specific."

The other scientists involved in this study were senior author Dr. George DeMartino, professor of physiology and former UT Southwestern postdoctoral fellows Dr. Eva Chin, now at Pfizer, and Dr. P. Darrell Neufer, now at Yale University.

The National Institutes of Health (NIH) Blood, Lung and Heart Institute and the NIH National Institute of Diabetes, Digestive and Kidney Diseases provided funding for the research.