Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Cell signaling discovery yields heart disease clues

26.09.2005


Hughes investigator John Scott long studied signal transduction system

A pulsing heart cell is giving Oregon Health & Science University researchers insight into how it sends and receives signals, and that’s providing clues into how heart disease and other disorders develop.

In a study appearing in today’s edition of Nature, John Scott, Ph.D., a Howard Hughes Medical Institute investigator and senior scientist at OHSU’s Vollum Institute, found that heart muscle cells become enlarged when an intricate intracellular signaling pathway regulated by a messenger molecule called muscle-specific A-kinase anchoring proteins, or mAKAPs, is perturbed.



The cells’ growth, known as cardiomyocyte hypertrophy, can lead to congestive heart failure and other forms of cardiovascular disease, which affect more than 70 million Americans and cause about 1.4 million deaths each year.

A cell communicates with another cell by sending over a messenger molecule, typically a hormone, which activates a secondary regulatory messenger molecule – cyclic AMP (cAMP) – within a particular compartment in the recipient cell. This causes cAMP to stimulate an enzyme that triggers the activity of proteins involved in altering a cell’s physiology and governing other biochemical events. According to Scott, mAKAPs tether the enzyme, called protein kinase A (PKA), to particular locations in the cell.

"Hypertrophy is a fairly good laboratory model for certain forms of heart failure, and the PKA signaling pathway is perturbed in certain cases of heart disease," said Scott, whose laboratory was the among the first in the world to track AKAP interaction. "That’s why this study may have a high translational and clinical impact."

According to the study, the mAKAP signaling system has been linked to excessive heart cell enlargement, which increases the potential for heart disease. One technique involves using drugs, such as a growth hormone, to activate a molecule known as ERK5, which suppresses the enzyme phosphodiesterase. This causes cAMP, which is normally metabolized by phosphodiesterase, to accumulate in certain parts of the cell.

"Many, many phosphodiesterases are drug targets," Scott noted. "So potentially, drugs that could target this particular phosphodiesterase, particularly, could be very useful. That’s still a long way away, but that’s where the work will go. Plus, it fits into a large body of work implicating these molecules as markers for certain forms of heart disease. Heart rate, for example, is controlled by calcium, and there’s some level of regulation by cyclic AMP as well."

To show the signal transduction process in a heart muscle cell, Scott and his colleagues used a fluorescent microscope that captures protein molecules stained with various colored dyes to show PKA activity in a cell. In one set of images, captured over six minutes, a greenish-yellow ring appears to expand around the cell’s nucleus before quickly shrinking. "That’s showing the rise in PKA activity, and the drop," Scott said.

Scott compares a cell to a highly organized city containing a variety of organizations serving particular functions, such as fire and police departments, an airport, a city hall and other entities. They all use one communication system, but information is delivered to, and interpreted by, each entity differently.

"The idea is that the cell is like this three-dimensional city, and at different times of the day, different things happen in the city," he explained. "This family of molecules we work on serves to pinpoint enzymes within three dimensions of the cell, and that’s very important because it means that these enzymes act very locally. What the imaging data in this paper shows is that not only do they work in three dimensions, but there’s this fourth dimension – time."

In addition, he said, "phosphodiesterase is a great drug target that could be something of importance in terms of pharmaceutical intervention at a later date."

Jonathan Modie | EurekAlert!
Further information:
http://www.ohsu.edu

More articles from Life Sciences:

nachricht New risk factors for anxiety disorders
24.02.2017 | Julius-Maximilians-Universität Würzburg

nachricht Stingless bees have their nests protected by soldiers
24.02.2017 | Johannes Gutenberg-Universität Mainz

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

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>