Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cystic fibrosis gene typo is a double whammy

15.11.2010
Researchers at the University of North Carolina at Chapel Hill School of Medicine have demonstrated that the gene mutated in cystic fibrosis not only controls traffic on the chloride highway, but also keeps the sodium highway from being overused.

An imbalance of salt and water in patients with cystic fibrosis makes their lungs clog up with sticky mucus that is prone to infection. The cause of the offending imbalance is a well-known genetic error, one that blocks the molecular expressway for tiny chloride ions to move across the surface of the lungs.

But how does that same gene mutation upset a parallel roadway controlling the flow of the other component of salt, sodium ions? Now, researchers at the University of North Carolina at Chapel Hill School of Medicine have found the answer, demonstrating that the gene mutated in cystic fibrosis not only controls traffic on the chloride highway, but also keeps the sodium highway from being overused.

The finding suggests that the infamous mutation – in a gene called CFTR – is a double whammy, affecting the flow of two different ions that are important to keep the mucus on the surfaces of the airways hydrated. Clarifying this link between the genetic defect and the thick sticky mucus in cystic fibrosis lungs could help researchers develop better therapies.

“It is very important to slow down this sodium channel when it is overactive before it leads to dehydration of the mucus in patient airways,” said Martina Gentzsch, PhD, assistant professor of cell and developmental biology at UNC and lead author of a study published Oct. 15 in the Journal of Biological Chemistry. “If we can understand the mechanism of how CFTR does that, it might give us a new approach to treat the disease.”

Cystic fibrosis is one of the most common genetic diseases in Caucasians, affecting approximately 1 in 3500 births in the United States. It is caused by a defect in the gene that codes for a protein called cystic fibrosis transmembrane conductance regulator or CFTR. Cystic fibrosis patients with the most severe disease have very little of the CFTR protein, and this affects the way chloride ions move across many tissues in the body. A number of scientists have hypothesized that CFTR also controls the movement of other ions, such as through the epithelial sodium channel or ENaC.

This channel has been shown to be overactive in transporting sodium ions in the airways of cystic fibrosis patients, so Gentzsch and her colleagues set out to determine why. First, they looked at the effects of the CFTR gene on the sodium channel in xenopus oocytes, commonly known as frog eggs. They found that when the CFTR gene was intact, the sodium channel was kept in check.

The researchers followed up with a number of biochemical and electrophysiological experiments and showed that the chloride channel and the sodium channels interact. Gentzsch and her colleagues also confirmed their results in human primary airway epithelial cells from healthy volunteers and patients with cystic fibrosis, showing that the sodium channel was in fact more active when there was no functional CFTR.

Now that they know that the chloride channel can actually influence the function of the sodium channel, Gentzsch is trying to find out how.

“We don’t know if it is doing this by basically acting like a roadblock, physically interfering with the proteases that activate ENaC, or if it is doing it by some indirect means,” said Gentzsch. “That is what we are investigating at the moment, so there are a lot of more questions to be answered.”

The research was funded by the National Institutes of Health and performed at the Cystic Fibrosis/Pulmonary Research and Treatment Center at the University of North Carolina, which also receives funding from the Cystic Fibrosis Foundation. Study co-authors include Richard C. Boucher, MD, director of the Cystic Fibrosis/Pulmonary Research and Treatment Center; and M. Jackson Stutts, PhD, professor of medicine.

Les Lang | EurekAlert!
Further information:
http://www.unc.edu

More articles from Life Sciences:

nachricht Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society

nachricht New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)

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

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>