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 NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation

nachricht Pollen taxi for bacteria
18.07.2018 | Technische Universität München

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First evidence on the source of extragalactic particles

For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.

To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...

Im Focus: Magnetic vortices: Two independent magnetic skyrmion phases discovered in a single material

For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.

Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...

Im Focus: Breaking the bond: To take part or not?

Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.

A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...

Im Focus: New 2D Spectroscopy Methods

Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.

"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....

Im Focus: Chemical reactions in the light of ultrashort X-ray pulses from free-electron lasers

Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.

Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Leading experts in Diabetes, Metabolism and Biomedical Engineering discuss Precision Medicine

13.07.2018 | Event News

Conference on Laser Polishing – LaP: Fine Tuning for Surfaces

12.07.2018 | Event News

11th European Wood-based Panel Symposium 2018: Meeting point for the wood-based materials industry

03.07.2018 | Event News

 
Latest News

NYSCF researchers develop novel bioengineering technique for personalized bone grafts

18.07.2018 | Life Sciences

Machine-learning predicted a superhard and high-energy-density tungsten nitride

18.07.2018 | Materials Sciences

Why might reading make myopic?

18.07.2018 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>