Nature Article: Roll of H2O2 in Cell Health…



An article in Nature Magazine earlier this year reveals new medical advances at Wake Forest University School of Medicine are helping scientists understand the complex role of hydrogen peroxide and regulating proteins in healthy cells.

Hydrogen peroxide is produced in the body to combat bacteria and keep cells healthy. But figuring out how the cells keep the H2O2 in check so that it doesn’t get carried away and damage the cell’s own tissues and DNA has been something of a puzzle.

New research coming from Wake Forest University is helping solve the puzzle and shedding new light on the complex and intricate relationships between various proteins and components working together to maintain healthy cells in the body.

W. Todd Lowther, Ph.D., leads the team which developed a three-dimensional snapshot of how two proteins produced by cells interact to regulate the levels of hydrogen peroxide.

Turns out, a molecule known as peroxiredoxin (Prx) helps control levels of hydrogen peroxide produced by cells in response to immune system activation. The Prx takes on the role of regulating the levels of hydrogen peroxide to protect the cells from over exposure to hydrogen peroxide; and even “switches” roles to send signals to alert the cell if the levels get too high and it cannot adequately handle the job.

Prx is busy regulating the levels of H2O2 in the cell, unless and until levels get dangerously high – at which point the Prx needs help. When that happens,
Prx stops converting hydrogen peroxide and instead changes roles to become an alarm system – signalling the cell to begin producing and activating other proteins to assist it in the reductiona nd removal dangerously higher levels of hydrogen peroxide.

According to Thomas J. Jonsson, Ph.D., “It basically acts as a sensor and warns the cell that levels are too high and that the cell needs to respond. Once that threat is gone, Prx needs to go back to its normal state.” Dr. Johnson is the lead author on the project and a post-doctoral fellow at Wake Forest.

But once Prx has given up its role as the regulator of H2O2, how does it revert back to that role?

In 2003, scientists reported that a protein known as sulfiredoxin (Srx) was involved in the process. The goal of Lowther’s team was to use X-ray crystallography to learn exactly what happens.

“This technology gives us a three-dimensional snapshot of how the proteins interact,” said Lowther. “We wanted to know how Prx changes its structure to be repaired.”

While the scientists knew the repair of Prx involved Srx, they didn’t know how the job was accomplished, and they didn’t know how the Prx would change, as they knew it would have to, to allow that repair to take place.

As it turns out, the answer is not only remarkable, but provides even more intimate understanding of the relationships of cell components and their interactions:

“We found that the protein unfolded, flipped around and attached to the back side of Srx, known as an ’embrace,'” said Lowther. “It basically put its arm around its buddy, which helps hold the repair protein in place.”

Jönsson said the binding of Srx causes a chemical reaction that repairs Prx. “The change in structure is dramatic and we found that it is critical for the repair to take place,” he said.

Understanding this protective mechanism that keeps cells healthy may one day help scientists identify how and when these processes go wrong resulting in disease. The research will continue to study Prx and how its changes in form and processing affects its interactions with other proteins.


The study was supported by the American Heart Association and National Institutes of Health. Lynnette C. Johnson, B.S., with Wake Forest, was a co-researcher.

Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. U.S. News & World Report ranks Wake Forest University School of Medicine 18th in family medicine, 20th in geriatrics, 25th in primary care and 41st in research among the nation’s medical schools. It ranks 35th in research funding by the National Institutes of Health. Almost 150 members of the medical school faculty are listed in Best Doctors in America.

Source: Shannon Koontz
Wake Forest University Baptist Medical Center

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