Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Major 'missed' biochemical pathway emerges as important in virtually all cells

27.05.2008
A new study by Duke University researchers provides more evidence that the nitric oxide (NO) system in the life of a cell plays a key role in disease, and the findings point to ways to improve treatment of illnesses such as heart disease and cancer.

The nitric oxide system in cells is “a major biological signaling pathway that has been missed with regard to the way it controls proteins,” and it is linked to cancer and other diseases when the system goes awry, said Jonathan Stamler, M.D., a professor of medicine and biochemistry at Duke University Medical Center who worked on the study.

In the body, nitric oxide plays a role in the transport of oxygen to tissues and physiological activities such as the transmission of nerve impulses, and the beating of the heart. When things go awry with the nitric oxide system, bad things can happen in bodies, according to recent studies. For instance, there may be too little nitric oxide in atherosclerosis and there may be too much in Parkinson’s disease; there may not be enough nitric oxide in sickle cell disease and there may be too much in some types of diabetes, Stamler said.

The new findings, which Stamler said change understanding of how the nitric oxide system is controlled, appear in the May 23 issue of the journal Science.

... more about:
»Heart »Oxide »Protein »Stamler »enzyme »nitric

“What we see now for the first time in the Science paper is that there are enzymes that are removing NO from proteins to control protein activity,” Stamler said. “This action has a broad-based effect, frankly, and probably happens in virtually all cells and across all protein classes. Nitric oxide is implicated in many disease processes. Sepsis, asthma, cystic fibrosis, Parkinson’s disease, heart failure, malignant hyperthermia -- all of these diseases are linked to aberrant nitric-oxide-based signaling.”

An important factor that previously wasn’t appreciated, he said, is that the target of nitric oxide in disease is different in every case. The finding of how nitric oxide binding to proteins is regulated opens the field for new refinement in biochemical research, said Stamler, who has been studying nitric oxide in cells for 15 years.

“Now we will need to study whether the aberrant cell signals are a matter of too much NO being produced and added to proteins or not enough being removed from proteins,” he said. “It is not simply a matter of too much or too little NO being in cells, but rather how much is being added or taken away from specific proteins, which is quite a different thing.”

First author on the paper, Moran Benhar, Ph.D., and co-author Douglas Hess, Ph.D., are both in the Duke Department of Medicine. Co-author Michael Forrester is a graduate student in the Duke Department of Biochemistry.

The research explains that the enzymes thioredoxin 1 and thioredoxin 2 remove nitric oxide from the amino acid cysteine within mammalian cells, thereby regulating several different actions in cells. One result of this removal is the activation of molecules that begin apoptosis, which is the normal programmed death of a cell. This process has potential importance for many diseases, including inflammatory diseases, heart failure and cancer. Because thioredoxins are established targets of drug therapy for arthritis, the research suggests potential therapeutic applications of the process.

The nitric oxide system is analogous to the much more studied phosphorylation system, in which phosphates are added and removed from proteins, the paper said. Changes in phosphorylation are among the most common causes of disease, and proteins that regulate phosphorylation are major drug targets, Stamler said.

“Aberrant dephosphosphorylation causes disease. Expect the same for denitrosylation,” Stamler said.

Similar research at Duke that was published in the journal Nature on March 16 supports Stamler’s findings. Christopher Counter, an associate professor in the Duke Department of Pharmacology and Cancer Biology, and colleagues found that eNOS (endothelial nitric oxide synthase), an enzyme that enhances the creation of nitric oxide, promoted tumor development and tumor maintenance in mice.

“The Chris Counter work is especially exciting because he shows that a nitric oxide synthase is linked to cancer, and he specifically identifies the protein that is the target of the nitric oxide, the protein that gets turned on through S-nitrosylation,” Stamler said. Blocking S-nitrosylation of this protein prevented cancer.

The steady stream of new papers on nitric oxide seems to underscore Stamler’s long-held belief that nitric oxide affects cells in bigger ways than many had appreciated. “When we began our studies two decades ago, we hypothesized that nitric oxide was part of a significant, broad-based system,” Stamler said. “Our hypothesis never changed.”

Mary Jane Gore | EurekAlert!
Further information:
http://www.duke.edu

Further reports about: Heart Oxide Protein Stamler enzyme nitric

More articles from Life Sciences:

nachricht New insights into the information processing of motor neurons
22.02.2017 | Max Planck Florida Institute for Neuroscience

nachricht Wintering ducks connect isolated wetlands by dispersing plant seeds
22.02.2017 | Utrecht University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Positrons as a new tool for lithium ion battery research: Holes in the electrode

22.02.2017 | Power and Electrical Engineering

New insights into the information processing of motor neurons

22.02.2017 | Life Sciences

Healthy Hiking in Smart Socks

22.02.2017 | Innovative Products

VideoLinks
B2B-VideoLinks
More VideoLinks >>>