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.
-end-
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

JCI Journals

Related Proteins Articles from Brightsurf:

New understanding of how proteins operate
A ground-breaking discovery by Centenary Institute scientists has provided new understanding as to the nature of proteins and how they exist and operate in the human body.

Finding a handle to bag the right proteins
A method that lights up tags attached to selected proteins can help to purify the proteins from a mixed protein pool.

Designing vaccines from artificial proteins
EPFL scientists have developed a new computational approach to create artificial proteins, which showed promising results in vivo as functional vaccines.

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.

Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.

Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.

Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.

Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.

Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.

Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.

Read More: Proteins News and Proteins Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.