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!
Polymers get caught up in love-hate chemistry of oil and water
28.02.2020 | DOE/Oak Ridge National Laboratory
How do zebrafish get their stripes? New data analysis tool could provide an answer
28.02.2020 | Brown University
Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.
The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...
Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics
Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...
Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.
A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...
The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.
Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...
Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.
Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...
12.02.2020 | Event News
16.01.2020 | Event News
15.01.2020 | Event News
28.02.2020 | Materials Sciences
28.02.2020 | Life Sciences
28.02.2020 | Architecture and Construction