Wasting away in muscle-ville

August 02, 2004

Loss of skeletal muscle tissue, termed cachexia, occurs in over half of cancer patients and, rather than tumor burden, is the direct cause of nearly one-third of cancer deaths. There are several regulatory proteins that are released from immune cells are known to be involved in the development of cachexia. These proteins are called cytokines and include TNF-a and IFN-g. The proteins in the muscles that are affected by these cytokines, however, remain largely unknown. Using both cell culture and animal models of cachexia, Denis Guttridge and colleagues, from the Ohio State University College of Medicine, investigated which the proteins in muscle that are altered the presence of cytokines, and discovered their target was surprisingly specific.

The authors examined several model protein targets of muscle wasting, including myosin heavy chain, actin, troponin, and tropomyosin. They found a striking specificity for the loss of myosin heavy chain only. Intriguingly, TNF-a/IFN-g-dependent loss of myosin heavy chain occurred through different mechanisms depending on whether they were examining it in cell culture or in a mouse model. In culture, loss of myosin heavy chain occurred through an RNA-dependent mechanism, while in tumor-bearing mice loss occurred through a protein breakdown process. The authors suggest that the choice of which mechanism reduces the amount of myosin heavy chain in cachexia may be related to the specific factor that is mediating muscle wasting. The identification that myosin heavy chain is such a selective target in cachexia may be useful in the design of future therapies for this major contributor to cancer patient death.
Author contact:
Denis C. Guttridge The Ohio State University College of Medicine, 420 W. Twelfth Ave. Columbus, OH 43210, USA Phone: 614-688-3137; Fax: 614-688-4006; E-mail: guttridge-1@medctr.osu.edu

View the PDF of this article at: http://www.jci.org/cgi/content/full/114/3/370

D. Grahame Hardie University of Dundee, Dow Street, Dundee, DD1 5EH, Scotland, UK Phone: 44-1382-344253; Fax: 44-1382-345783; E-mail: d.g.hardie@dundee.ac.uk

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