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Role Of Hydrogen Peroxide In Cell Health Explored

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Role Of Hydrogen Peroxide In Cell Health Explored

http://www.medicalnewstoday.com/articles/92949.php

Hydrogen peroxide, the same mild acid that many people use to

disinfectant their kitchens or treat cuts and abrasions, is also

produced by the body to keep cells healthy. Now, researchers at Wake

Forest University School of Medicine have solved how part of this

complex process works.

Reporting in the January 3 issue of Nature, a team led by W. Todd

Lowther, Ph.D., developed a three-dimensional snapshot of how two

proteins produced by cells interact to regulate the levels of

hydrogen peroxide.

For example, when the immune system is activated in response to

bacteria, large amounts of hydrogen peroxide are produced by certain

cells to fight the infection. Lowther and colleagues studied how a

molecule known as peroxiredoxin (Prx) helps control levels of the

agent. The role of Prx is important because if the levels of

hydrogen peroxide become too high, the cell's DNA and other proteins

can be damaged. Scientists suspect that this and similar processes

are what leads to cancer, diabetes and other disease.

Prx actually has a dual role in the process. Its usual job is

removing excess hydrogen peroxide from the cells by converting it to

water. But if levels get dangerously high - and Prx needs help - it

becomes inactive in its " converting " job and instead becomes

a " signaler, " telling the cell to produce or activate other proteins

to help remove the excess.

" It basically acts as a sensor and warns the cell that levels are

too high and that the cell needs to respond, " said J.

Jönsson, Ph.D., lead author, and a post-doctoral fellow at Wake

Forest. " Once that threat is gone, Prx needs to go back to its

normal state. "

But how does Prx revert back to its usual job and become active

again, so that it is available for a new wave of hydrogen peroxide?

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. "

The scientists knew that the repair of Prx would involve it binding

with Srx. They also knew that the structure of Prx would need to

change because the portion of the molecule that is repaired by Srx

is initially hidden when it is in the inactive form.

" 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.

The scientists said that understanding this protective mechanism

that keeps cells healthy may one day help reveal how the process

goes awry in disease. They will continue the research by studying

how the structural change may affect how Prx interacts with other

proteins.

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