Scientists discover genetic pathway crucial to disease, aging

February 21st, 2008 - 1:47 pm ICT by admin  

London , Feb 21 (ANI): Scientists at the University of Wisconsin-Madison have cited in a study that a chemical reaction similar to iron-rusting is responsible for many human diseases ranging from Alzheimer’s, heart disease and stroke to cancer and the inexorable process of aging.

According to the scientists, this process, known as oxidative stress, eats up healthy cells in the body and leads to these diseases. They have discovered a gene expression pathway that has a great effect on the process of oxidative stress.

The results of this study led by Richard A. Anderson, a UW-Madison professor of pharmacology at the UW School of Medicine and Public Health, are important as it has future implications in the manipulation of genes or the development of novel drugs to combat disease.

“Most of the genes this pathway controls are important for human disease. This is a totally new and novel pathway that controls the synthesis of enzymes key for many human diseases,” Nature quoted Anderson , as saying.

Oxidative stress is due to the overworking of the body’s ability to neutralize highly toxic chemicals known as free radicals, which can damage DNA and other molecules pivotal for the health of a cell.

Theres a key enzyme in the new pathway, dubbed Star-PAP by its discoverers, that works as part of a complex that managing the expression of messenger RNA (mRNA), all-important molecules that carry genetic information from the nucleus of a cell to the cytoplasm where proteins are made. Star-PAP aids in adding a critical biochemical tail onto mRNA that is needed for the stability of the mRNA molecules. In a kite-like fashion this tail can turn mRNAs on and off, and governs the production of certain key enzymes and proteins in the cell.

“The tai lis 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,” explained Anderson .

According to Anderson , the Star-PAP enzyme controls the production of a very small number of proteins and enzymes in cells, but they have effects that go beyond oxidative stress. However, it was found that this novel pathway has 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. A wealth of the genes involved in oxidative stress also seems to be the direct targets for the Star-PAP pathway,” said Anderson .

He said hat this discovery has important clinical relevance as it sis possible to manipulate the pathway for highlighting 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,” said Anderson.

It is possible for oxidation to damage DNA, mitochondria, cell membranes, and other mechanisms and structures essential to the cell. Such damage supports 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,” said Marvin Wickens, a UW-Madison biochemist who was not involved in the study.

The stress leading to the disease can be greatly reduces by new drugs that modulate the enzyme and control its activity.

“We’ve discovered a novel pathway that controls expression of genes important to oxidative stress. 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, said Anderson.

The study is published in the current edition of the journal Nature. (ANI)

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