Broken Hearts: Aggies Probe Biochemistry of Cardiovascular Disease

In the popular television series Big Bang Theory, socially challenged physicist Sheldon Cooper is reluctant to enter a blueberry pie-eating contest.

“With all those antioxidants,” he implores. “What if I run out of oxidants?”

Not likely, say Utah State University biochemists. While humans depend on oxygen for survival, the life-saving element exacts a toll on our bodies. Ironically, they say, as long as you’re taking in oxygen, you’re at the mercy of the chemistry of life.

“Oxidation in our bodies is a normal part of aging,” says Joanie Hevel, associate professor in USU’s Department of Chemistry and Biochemistry. “Oxidizing agents in our bodies contribute to the havoc.”

During normal metabolism, free radicals and other oxidants form as oxygen fuels our cells. Chemicals with antioxidant properties in our bodies help to keep free radicals in check, but sometimes have trouble keeping a healthy balance — a condition known as oxidative stress.

Hevel and her students study a class of enzymes called Protein arginine N-methyltransferases or “PRMTs” that are affected by oxidative stress. Dysfunction of these enzymes is thought to contribute to a number of human ailments, including cardiovascular disease, cancer, kidney disease and diabetes.

Hevel’s doctoral student Yalemi Morales is lead author on a paper published June 12, 2015, in the Journal of Biological Chemistry, which explores whether or not oxidative stress leads to increased expression of the enzyme PRMT1 and a resultant accumulation of asymmetric dimethylarginine or “ADMA.” Other authors on the paper include Hevel and USU students Damon Nitzel, Owen Price and Shanying “Laurel” Gui, as well as Jun Li and Jun Qu of the State University of New York, Buffalo.

ADMA is a naturally occurring chemical found in blood plasma. Elevated levels of ADMA correlate with risk factors for cardiovascular disease.

“When we treated PRMT1 with oxidants, we expected increased enzymatic activity and a corresponding increase in ADMA,” says Morales, a recipient of a USU School of Graduate Studies Dissertation Fellowship. “But we saw the opposite result of what you might expect.”

The researchers found PRMT1 is impaired under oxidative conditions and actually displays decreased activity. Further, they found inhibited PRMT1 activity is readily reversed by use of antioxidants.

“Our results challenge the unilateral view that increase PRMT1 expression necessarily results in increased ADMA synthesis,” Morales says. “In addition, our results demonstrate that enzymatic activity can be regulated in a redox-sensitive manner.”

The role of PRMT1 activity in the oxidative stress response, she says, may be more complex than previously thought.

The Hevel team, whose research is supported by the National Science Foundation, plans further investigation of the enzymes. Better understanding of PRMTs, they say, could aid efforts to develop new drugs to inhibit cardiovascular disease and other 21st Century scourges.

Editor’s Note: Morales was among students highlighted in a “Meet the New Aggies” feature, when she transferred to Utah State from the University of Nevada, Las Vegas in 2007. The Cuban-born scientist was, incidentally, the university’s first transfer student to be selected as a USU Undergraduate Research Fellow. Now a doctoral candidate, Morales served as president of USU’s recently established chapter of the Society for Advancement of Hispanics/Chicanos and Native Americans in Science. As a SACNAS officer, she’s mentored aspiring scientists through Science Unwrapped, the Biotechnology Summer Academy, the Native American Mentorship Program and more.

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