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Protein controls acid in cells by direct detection of volume changes, study finds

DALLAS July 5, 2004 A protein responsible for regulating acid levels within cells and pumping out acid accumulated in cardiac cells after a heart attack activates in direct response to changes in a cell's volume, according to a new study by researchers at UT Southwestern Medical Center at Dallas.

Their findings show that the protein NHE1, which is found in the membranes of nearly all cells and is especially active in cancer cells, is regulated by the stretch and pull of the membrane as a cell changes volume. The study appears in the Proceedings of the National Academy of Sciences and is available online.

NHE1, which is called a transporter protein, oscillates its shape rapidly in a cell's membrane. This allows sodium from the outside to come in and protons positively charged particles from inside the cell to escape and lower the cell's acidity. The fewer protons in a cell, the less acidic it is.

"The acidity in the cell is a huge signal for the cell," said Dr. Donald Hilgemann, professor of physiology at UT Southwestern and senior author of the study. "The control of acidity regulates cell growth and proliferation."

Hormones and many other signals that control cell growth and proliferation act on NHE1, he said.

"Our study shows that as cell volume increases, this transporter turns off. If volume decreases, it turns on by directly sensing mechanical changes in the membrane," continued Dr. Hilgemann.

The NHE1 transporter is a protein of much interest to drug developers investigating ways to prevent cell death, which often accompanies heart attacks and strokes. In ischemia, where the blood supply is cut off to cardiac cells or brain cells, cells become very acidic. As the body's normal metabolism gets going again, the NHE1 system starts pumping out the accumulated acid, exchanging the acid for sodium.

"It's such an active system that you can overload the cell with sodium," Dr. Hilgemann said. "Too much sod
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Contact: Amanda Siegfried
amanda.siegfried@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
5-Jul-2004


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