Apr. 22, 1998 SAN FRANCISCO--Sodium transport - the kidney function that regulates the level of salt in the kidney and bloodstream and, ultimately, blood pressure, may be intimately related to some of the same oncogenes that have been implicated in the unchecked cellular growth of cancer. Douglas Eaton, Ph.D., associate professor of physiology and pediatrics at Emory University and director of Emory's Center for Cell and Molecular Signaling, presents the findings at the Experimental Biology '98 Meeting in San Francisco on Monday.
Dr. Eaton and his colleagues examined genetic, hormonal and pharmacologic changes that affect the sodium channels, which are special protein molecules found in a type of kidney cell. Sodium channels act as a gatekeeper by retaining salt in the kidney or by allowing it to enter the bloodstream in response to changes in blood pressure. Small alterations in these molecules cause them to retain too much salt, which can lead to high blood pressure. About 30 percent of people who have hypertension, or high blood pressure, are reacting to the buildup of too much sodium.
"If the sodium channels are too active," says Dr. Eaton, "then people retain sodium, causing water buildup and an abnormal rise in blood pressure."
Hypertension affects an estimated 62 million Americans and is an underlying cause of heart attacks, heart failure and strokes, as well as kidney failure. Some people have a specific, genetic abnormality that affects the sodium channels, but in other people there is nothing obviously wrong.
"In this other group of people, the sodium channels are switched on or off incorrectly by another molecule," says Dr. Eaton.
The steroid hormone aldosterone regulates how much sodium is released or retained by the sodium channels. In turn, steroid hormones like aldosterone work by switching on and off other proteins. Dr. Eaton and his colleagues have found that one of those other proteins is the oncogene, p21 ras, which has been implicated in a variety of cancers.
"It was a complete surprise to us that an oncogene implicated in cancer development would also be used to turn on and off the function of a sodium transport cell," notes Dr. Eaton. In addition, he and his colleagues have found that another oncogene - src kinase, is also responsible for regulating the actions of sodium channels in some individuals.
Learning how the kidney cells communicate and how they are regulated to maintain the complex balance of salt and fluid will help researchers better understand how kidney diseases begin and how hypertension might be controlled more successfully.
The research was supported by a grant from the National Institutes of Health.
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