Inducible Protein Protects Muscle Tissue from Chronic Disease-Related Atrophy

An isoform of the protein PGC-1alpha (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) that stimulates muscle growth has been found to be induced in muscle by exercise and to protect muscle tissue from wasting due to chronic diseases such as cancer.

PGC-1alpha interacts with, and regulates the activities of, cAMP response element binding protein (CREB) and nuclear respiratory factors (NRFs). It provides a direct link between external physiological stimuli and the regulation of mitochondrial biogenesis, and is a major factor that regulates muscle fiber type determination. This protein may be also involved in controlling blood pressure, regulating cellular cholesterol homoeostasis, and the development of obesity.

Investigators at Dana-Farber Cancer Institute (Boston, MA, USA) used advanced genetic engineering techniques to transfect the muscle tissue of a mouse population with the gene for the PGC-1alpha isoform, PGC-1alpha4.

They reported in the December 7, 2012, issue of the journal Cell that this protein specifically induced the muscle growth factor IGF1 (insulin-like growth factor 1), while repressing the inhibitor of muscle growth, myostatin. Within several days of insertion of PGC-1alpha4 into the leg muscles of mice by a viral carrier, muscle fibers were found to be 60% larger than those in untreated mice were. The modified mice were 20% stronger and more resistant to fatigue than the control animals, and they were leaner than the normal mice.

The genetically engineered mice showed significantly enhanced resistance to cachexia (chronic disease-related muscle wasting). The modified mice lost only 10% mass in a leg muscle compared to a 29% loss in mice with cancer that did not express additional PGC-1alpha4.

“All of our muscles have both positive and negative influences on growth,” said senior author Dr. Bruce Spiegelman, professor of cell biology at Dana Farber Cancer Institute. “This protein (PGC-1alpha4) turns down myostatin and turns up IGF1. It is pretty amazing that two proteins made by a single gene regulate both effects.”

Related Links:
Dana-Farber Cancer Institute