Genetic pathway critical to disease, a...(ns is like a postage stamp that enables...)

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."

The discovery of a gene expression pathway and specific enzymes that exert broad influence on the process of oxidative stress has clear clinical relevance, Anderson says, because it could potentially be manipulated to mitigate the damage oxygen does to cells.

"Oxidative stress control pathways for us humans are pretty important because we live in an environment where oxygen is required to keep us alive, but also stresses us because of oxidative damage to our cells," Anderson says.

Oxidation can damage DNA, mitochondria, cell membranes, and other mechanisms and structures essential to the cell. Such damage underpins disease, including in the parts of the body -- the heart, the lungs and the brain -- that are heavy users of oxygen.

"We'll be able to get at this new machinery and, hopefully, manipulate it," says Marvin Wickens, a UW-Madison biochemist who was not involved in the study. New drugs that modulate the enzyme and control its activity could potentially blunt the stress that leads to disease.

Although the discovery of a new genetic pathway in cells is important, much work remains to identify how the pathway inf
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