( Scientists at the Salk Institute for Bi...)Salk scientists hammer out a pathway that promotes muscle cell survival in mice

Scientists at the Salk Institute for Biological Studies have identified an enzyme that pumps up a cell’s ability to maintain healthy muscle and restores normal muscle function in genetically engineered mice with weak muscles. The study, published online in Nature Medicine, is the first to explore the part this enzyme plays in a cascade of events triggered by exercise-induced hormones and other signals.

In this particular pathway, a molecular switch turns on a set of muscle-specific genes in response to exercise by releasing a brake that normally keeps these genes off. Learning how this pathway affects cellular responses may provide clues for improving cellular health in diseases affecting muscle and other cell types.

"In addition to muscle, this regulatory circuit is present in brain and heart tissue, where it also seems to control cell survival," said Marc Montminy, M.D., Ph.D., professor in the Clayton Foundation Laboratories for Peptide Biology at the Salk Institute and senior author of the study. "Therefore, we believe that understanding the role of this enzyme in muscle cells may someday shed light on the underlying mechanisms of many diseases that affect cell survival, such as muscular dystrophy, neurodegenerative diseases, and congestive heart failure."

Montminy’s team, led by postdoctoral researcher Rebecca Berdeaux, Ph.D., first became interested in the enzyme when they observed that mice engineered to have a defect in a molecular switch, called cAMP responsive element binding protein (CREB), had hunched backs, muscle wasting, and other signs of unhealthy muscles. Although CREB had long been studied for its role in glucose regulation in metabolic tissues like the liver and pancreas, its function in muscle tissue was unknown. Then, the researchers noticed that mice lacking CREB activity in their muscle cells also had a genetic brake, called histone deacetylase (HDAC), stuck in place. Without loosening the brake by a chemical mod
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Source:Salk Institute

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