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The actions of NO in this experiment also resemble the process by which oxygen affects cell health and disease, the scientists say.

"Now we have demonstrated that an NO group, attached to a thiol within a cell, has regulatory function," Stamler said. "There has been growing evidence that NO does its work in the body by signaling genes, but no one has found proof before this."

Both oxygen and NO are vital to life processes, but too much of either can damage cells. To keep the amount of oxygen and NO in balance, cells have built-in systems to eliminate the excess. One way to do that is to have transcription factor sensors that get turned on when too much oxygen or NO is present.

In fact, bacterial cells attempt to control both excess oxygen and excess nitrogen with the same OxyR transcription factor.

In human cells, constant vigilance against excess oxygen and NO takes a toll over time. When the system is out of balance, perhaps when a transcription factor is mutated, disease can result, the scientists say.

"It is a parallel process to what is known as oxidative stress, in which an excess of oxygen in cells can lead to a host of diseases, as well as the cumulative damage we call aging," Stamler said. "NO has a similar deleterious function, which we call nitrosative stress. When a cell can't contain the flow of SNO, the nitrosative stress can well be theorized to contribute to cancer, arthritis, neurodegenerative diseases, stroke and hardening of the arteries -- all diseases associated with NO."

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Contact: Karyn Hede George
georg016@mc.duke.edu
919-660-1301
Duke University Medical Center
14-Aug-1996


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