November 7, 2013
Faulty Enzymes At The Heart Of Diabetic Cardiomyopathy
redOrbit Staff & Wire Reports - Your Universe Online
A family of enzymes that controls the functions of other proteins could be the possible cause of heart failure in diabetics, according to new research appearing in the Journal of Biological Chemistry.While many studies have been written on cardiovascular disease and diabetes, little is known about diabetic cardiomyopathy, a disorder of the heart muscle in diabetes patients that can lead to the heart’s inability to effectively circulate blood throughout the body.
Now, researchers from the University of Texas Medical Branch at Galveston (UTMB) have reportedly discovered one of the potential causes of the condition: protein kinase C (PKC), which manages the function of other proteins by using phosphates to activate or deactivate them.
UTMB assistant professor of biochemistry Dr. Muge Kuyumcu-Martinez and colleagues analyzed the effects of PKC signals in the hearts of diabetic mice, and concluded that “the leading cause of diabetic cardiomyopathy can be attributed to PKC activation and its downstream effects on gene expression.”
“Knowing how cardiomyopathy manifests, further research can use these results to concentrate on the prevention and treatment of heart failure in diabetics,” she added. Experts from the University of California, San Diego and Academia Sinica in Taipei also contributed to the research.
Cardiomyopathy is a known symptom of diabetes that occurs when the heart muscles weaken and the heart no longer has the strength to pump blood through the body. According to the researchers, diabetic adults are between two and four times more likely to die of heart failure than their non-diabetic counterparts.
Dr. Kuyumcu-Martinez and her co-authors found that when PKC becomes over-activated, adult heart cells begin using splicing methods originally utilized during the embryonic stages. A person’s DNA contains codes for specific biological processes and products, and they use messenger RNA to send signals to the body to complete those tasks, according to the research team.
Alternative splicing occurs when a single gene contains codes for more than one protein, they added. Since the human genome contains 20,000 protein-coding genes, they point out that using one gene to create multiple proteins is an efficient process when things are working correctly.
However, when genetic information is abnormally spliced or mis-spliced to messenger RNA, it means that the instructions become mutated. Up to 33 percent of all genetic diseases can be attributed to these types of splicing errors, as can many different types of cancer, noted Kuyumcu-Martinez' team.
“In the case of diabetic cardiomyopathy, the research team used RNA sequencing technology to identify 22 specific alternative splicing events that occur, causing a developmental shift in the gene expression,” the researchers explained. “This shift causes mechanisms of the heart to behave as though it were still an embryo, which prevents the heart from functioning correctly in a full-grown adult fighting diabetes.”