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EMBO Molecular Medicine

All articles accepted from 14 August 2012 are published under the terms of the Creative Commons Attribution License.   Articles accepted before this date were published under the agreement as stated in the final article.

Cover image for Vol. 7 Issue 10

Edited By: Stefanie Dimmeler (Chief Editor), Roberto Buccione and Céline Carret (EMBO Editors)

Online ISSN: 1757-4684

Protein discovery in muscle could benefit conditions that cause muscle loss

November 2012

EMBO Molecular Medicine - Protein discovery in muscle could benefit conditions that cause muscle loss

Hibernation research yields clues in muscular dystrophy, cancer, immobility

Loss of muscle mass makes a bad situation worse for individuals coping with immobility, cancer, other illnesses, and more than 500 genetic conditions. When muscle fibres fail to maintain their normal cycle of growth and regeneration, inactivity and atrophy can trigger devastating consequences such as pneumonia, pressure ulcers, falls, and permanent immobility.

Research announced today shows that a protein whose roles in many of the body’s systems are already understood is also vital in maintaining muscle mass. This opens up a new research pathway for prevention and treatment of muscle atrophy in many inherited conditions and acquired illnesses, says lead author Dr. Ronald D. Cohn. He is head of the Division of Clinical & Metabolic Genetics and co-director of the new Centre for Genetic Medicine at The Hospital for Sick Children (SickKids), and Associate Professor of Paediatrics at University of Toronto. The study appears today in the Early View edition of EMBO Molecular Medicine.

Clues in hibernation

Dr. Cohn and his international co-investigators first identified the critical role of the SGK1 protein in animals’ resumption of normal activity following hibernation. The team then studied the protein’s effects on muscle tissue. While SGK1 (serum glucocorticoid-induced kinase-1) is widely known for its complex roles in cardiovascular, kidney, and other functions, the fact that it also plays a vital role in regulating muscle mass in mammals has not been known until now.

"Previous research of hibernating animals has yielded important insights into many aspects of metabolism," says Dr. Cohn. "Our team is engaged in the question of how animals recover full use of skeletal muscles that atrophy due to illness, decreased caloric needs, or inactivity.

We found that SGK1 is critical in hibernating ground squirrels. Building on that insight, we wondered if SGK1 plays a role in the muscle cells of non-hibernating mammals. We now confirm that, along with the protein Akt, it plays a vital role in muscle homeostasis – that is, maintaining functional muscle mass and preventing muscle loss in conditions leading to muscle atrophy."

The researchers showed that leg muscles in mice that do not have normal levels of SGK1 develop more severe atrophy compared to normal mice. On the other hand, when mice are inactive or on a calorie-reduced diet, a boost of SGK1 protects them from muscle loss or atrophy.

Muscle-mass regulator

"Until now, we have understood the protein Akt to be the primary muscle-mass regulator," Dr. Cohn says. The discovery that SKG1 also plays a critical role opens up the potential for research that could help to sustain muscle mass in old age, illness, immobility, spinal cord injury, and some neuromuscular conditions.

"It’s much too soon to predict a clinical impact for this research. At the same time, we are optimistic about the potential for eventual applications that could make a difference in the physical status and quality of life of people who suffer from muscle loss," says Dr. Cohn. "Our next projects will focus on applying this new understanding of SKG1 to conditions associated with denervation (such as spinal cord injury) and genetic conditions such as the many types of muscular dystrophy," he adds.

The project was an international effort involving 23 researchers in Spain, France, and several centres in the U.S. and Germany. Dr. Cohn and partners initiated and completed this research when he was at Johns Hopkins University School of Medicine in Baltimore.

Funding support included the (U.S.) National Institutes of Health and the Dana and Albert R. Broccoli Charitable Foundation for Research.

Activation of serum/glucocorticoid-induced kinase 1 (SGK1) is important to maintain skeletal muscle homeostasis and prevent atrophy
Eva Andres-Mateos, Heinrich Brinkmeier, Tyesha N. Burks, Rebeca Mejias, Daniel C. Files, Martin Steinberger, Arshia Soleimani, Ruth Marx, Jessica L. Simmers, Benjamin Lin, Erika Finanger Hedderick, Tom G. Marr, Brian M. Lin, Christophe Hourdé, Leslie A. Leinwand, Dietmar Kuhl, Michael Föller, Silke Vogelsang, Ivan Hernandez-Diaz, Dana K. Vaughan, Diego Alvarez de la Rosa, Florian Lang, Ronald D. Cohn
EMBO Molecular Medicine 2012, 4, Early View

Provided by SickKids