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."
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 influences human disease, Anderson says.
"We've discovered a novel pathway that controls expression of genes important to oxidative stress," he says. "It has really key implications for heart disease, stroke, and possibly for aging, but it is still not clear precisely what functions this pathway is regulating in the context of those conditions."
Richard Anderson | EurekAlert!
Zap! Graphene is bad news for bacteria
23.05.2017 | Rice University
Discovery of an alga's 'dictionary of genes' could lead to advances in biofuels, medicine
23.05.2017 | University of California - Los Angeles
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
In the race to produce a quantum computer, a number of projects are seeking a way to create quantum bits -- or qubits -- that are stable, meaning they are not much affected by changes in their environment. This normally needs highly nonlinear non-dissipative elements capable of functioning at very low temperatures.
In pursuit of this goal, researchers at EPFL's Laboratory of Photonics and Quantum Measurements LPQM (STI/SB), have investigated a nonlinear graphene-based...
Dental plaque and the viscous brown slime in drainpipes are two familiar examples of bacterial biofilms. Removing such bacterial depositions from surfaces is...
23.05.2017 | Event News
22.05.2017 | Event News
17.05.2017 | Event News
23.05.2017 | Physics and Astronomy
23.05.2017 | Life Sciences
23.05.2017 | Medical Engineering