Tracking a Deteriorating Heart; A Salivary Proteome

Story Ideas from the March 2008 Issue (Vol. 7, No. 3)

Tracking a Deteriorating Heart

Researchers have conducted a detailed molecular survey of how heart muscle proteins change over time in diseased tissue, revealing clues that may lead to earlier diagnosis of heart disease.

Despite great progress in reducing mortality, cardiomyopathies (diseases affecting heart muscle) remain one of the leading killers in the developed world. A big contributor to this mortality is that many patients only get diagnosed at later disease stages, limiting therapeutic options.

Tony Gramolini, Andrew Emili and their colleagues sought to obtain more insight into cardiomyopathy progression, so they performed a large-scale protein survey of mouse cardiac cells affected by a mutation that weakens the muscle. They compared protein profiles at 8, 16, and 24 weeks of both diseased and healthy animals.

The researchers noticed time-dependent changes in 593 proteins, around 40 of which were particularly strong. While the altered proteins affect a variety of biological pathways, an inability to maintain the proper calcium balance, leading to increased cell stress, was heavily affected. Restoring this balance might be a key to treating these heart conditions early on.



Heart sections of normal and R9C mice reveal significant cardiac enlargement, even at the earliest time point 

Corresponding authors: 
Andrew Emili, Donnelly Centre for Cellular and Biomedical Research, University of Toronto, Ontario; Tel: (416) 946-7281 / Email: andrew.emili@utoronto.ca

Anthony O. Gramolini, Charles H. Best Institute, University of Toronto, Ontario; 
Tel: (416) 978-5609 / Email: anthony.gramolini@utoronto.ca



Understanding Our Saliva

Researchers have developed a novel technique to separate and analyze all the proteins found in human saliva, not just the soluble ones, providing an approach that may reveal protein markers for oral cancer and other disorders in the oral cavity.

Saliva contains an abundance of proteins that could be used to screen for diseases, particularly oral diseases. Until now, though, studies have only focused on the small subset of free-floating saliva proteins. Far more proteins are present inside of oral cells, and Timothy Griffin, Nelson Rhodus and colleagues developed a method, called three-step peptide fractionation, to look at those understudied proteins. 

They analyzed saliva samples from four oral cancer patients and identified over 1000 human proteins, including many known cancer associated proteins. In addition, they separated out proteins from over 30 different bacteria, many of which have not been previously found in saliva, and several of which may also have possible cancer links.

The researchers note that the mortality rate for oral cancer has hardly declined over the past 30 years; their technique, providing the first description of using whole cells to identify the vast array of human and bacterial proteins in saliva, may help identify new markers for oral cancer progression.

Corresponding Authors: 
Timothy Griffin, Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis; Phone: 612-624-5249, Email: tgriffin@umn.edu

Nelson Rhodus, Division of Oral Medicine, School of Dentistry, University of Minnesota,
Minneapolis; Phone: 612-625-0693, Email: rhodu001@umn.edu