The same chemical reaction that causes iron to rust plays a similarly corrosive role in our bodies.
Oxidative stress chips away at healthy cells and is a process, scientists know, that contributes to a host of diseases and conditions in humans ranging from Alzheimer's, heart disease and stroke to cancer and the inexorable process of aging.
Now, writing in the current edition (Feb. 21, 2008) of the journal Nature, a team of University of Wisconsin-Madison scientists reports the discovery of a gene expression pathway that exerts a sweeping influence over the process of oxidative stress.
The finding is important because at its foundation it represents a master pressure point for a host of medical conditions, and could one day enable the manipulation of genes or the development of novel drugs to thwart disease.
"Most of the genes this pathway controls are important for human disease," according to Richard A. Anderson of the UW School of Medicine and Public Health and senior author of the new Nature report. "This is a totally new and novel pathway that controls the synthesis of enzymes key for many human diseases."
Oxidative stress occurs when the body's ability to neutralize highly toxic chemicals known as free radicals is overtaxed. Free radicals can damage DNA and other molecules essential for the health of a cell.
A key enzyme in the new pathway, dubbed Star-PAP by its Wisconsin discoverers, functions as part of a complex that controls the expression of messenger RNA, all-important molecules that carry genetic information from the nucleus of a cell to the cytoplasm where proteins are made. Star-PAP is responsible for adding a critical biochemical tail onto messenger RNA. The tail, in kite-like fashion, is necessary for the stability of the messenger RNA molecules, can turn them on and off, and thus governs the production of certain key enzymes and proteins in the cell.
"The tail," Anderson explains, "is like a postage stamp that enables messenger RNA to exit the nucleus of the cell and enter the cytoplasm where the genetic message is translated into protein."
The Star-PAP enzyme regulates the production of a relatively small number of proteins and enzymes in cells, but those could have an influence far beyond oxidative stress, Anderson notes. However, the Wisconsin group found that the newfound pathway contains a genetic "on-off" switch for a key protein known as heme oxygenase-1, an agent that protects cells from oxidative stress.
"Star-PAP is a master switch that controls key aspects of oxidative stress in cells," says Anderson, a UW-Madison professor of pharmacology. "A wealth of the genes involved in oxidative stress also seems to be the direct targets for the Star-PAP pathway."