Navigation Links
Newly Discovered Role for Heart Response Enzyme May Yield Better Heart Failure Therapy

Duke University Medical Center researchers have identified a new protein that plays a critical role in enabling the heart to respond to such external stimuli as exercise or stress, as well as in the progressive loss of heart function that is heart failure, the researchers said.

Their findings, they said, suggest new approaches to prevent or reverse heart failure, which affects two to three million people in the U.S. The team reports its findings in the August 2005 issue of Nature Cell Biology. The study is now available as an advance online publication.

"We've uncovered new details of the first step of heart failure, in which heart receptors that normally allow the heart to adapt in the face of changing conditions are lost, rendering the heart unable to pump enough blood to meet the needs of the body's other organs," said cardiologist and geneticist Howard Rockman, M.D., of Duke. "If we could prevent this loss of heart receptors, we might improve heart function in patients with heart failure."

The enzyme the researchers studied, called phosphoinositide 3-kinase (PI(3)K), governs the function of beta-adrenergic receptors on the surface of heart cells. Such receptors are protein switches that nestle in the cell membrane and that are activated by the hormone adrenaline to enhance the heart's pumping action in response to exercise or stress.

In heart failure patients, chronic stress leads to an excess of adrenaline, over-stimulating beta-adrenergic receptors, a process that results in receptor desensitization and loss, Rockman said.

Earlier work by Rockman's team identified PI(3)K as being required for beta-adrenergic receptors to be drawn back into the cell for recycling once they have been activated. Those studies showed that increases in PI(3)K underlie the loss of beta-adrenergic receptors in animals and patients with heart failure, Rockman said.

The researchers' earlier experiments showed that disrupting the function o f PI(3)K preserves beta-adrenergic receptors on heart cells when they are chronically exposed to adrenaline and thus preserves heart function. However, it has remained unclear exactly how the heart enzyme exerts its effects on the heart receptors, Rockman added.

The researchers' experiments revealed that PI(3)K plays multiple roles as an enzyme that affect heart responses. It manufactures signaling molecules called phospholipids in the cell. And it activates other molecules, among them one called "non-muscle tropomyosin," which plays an important role in maintaining cell structure. In both cases, PI(3)K functions by attaching a phosphate group to the molecule to be activated, a process called phosphorylation.

By preventing activation of tropomyosin by PI(3)K in cells, the researchers prevented heart receptors from leaving the cell surface, thereby blocking the initial step that occurs during heart failure. Also, the researchers reported, when they eliminated tropomyosin activity altogether, they also maintained heart receptors.

"These studies demonstrate a previously unknown role for the protein phosphorylation activity of PI(3)K in receptor internalization and identify non-muscle tropomyosin as an important substrate of the enzyme's activity," Rockman said. "The findings may offer a new approach to the treatment of heart failure."

Drugs that selectively prevent PI(3)K from activating tropomyosin -- either by modifying tropomyosin or inhibiting PI(3)K's enzymatic activity -- might effectively block heart receptor loss to maintain or restore normal heart function in those at risk or suffering from heart failure, he added.

Collaborators on the study include Sathyamangla Naga Prasad, Arundathi Jayatilleke and Aasakiran Madamanchi, all of Duke. The work was supported by the National Institutes of Health.


'"/>

Source:Duke Health


Related biology news :

1. Newly-discovered class of genes determines ?and restricts ?stem cell fate
2. Newly discovered virus linked to childhood lung disorders and Kawasaki disease
3. Newly Discovered Compound Blocks Known Cancer-Causing Protein
4. Newly discovered pathway might help in design of cancer drugs
5. Newly Discovered Branding Process Helps Immune System Cells Pick Their Fights
6. Newly discovered protein an important tool for sleeping sickness research
7. Newly discovered genetic disease sheds light on bodys water balance
8. Newly recognized gene mutation may reduce seeds, resurrect plants
9. Newly discovered birdlike dinosaur is oldest raptor ever found in South America
10. Fitting in: Newly evolved genes adopt a variety of strategies to remain in the gene pool
11. Newly identified mechanism helps explain why people of African descent are more vulnerable to TB
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/26/2016)... India and LONDON ... Infosys Finacle, part of EdgeVerve Systems, a product ... and Onegini today announced a partnership to integrate ... solutions.      (Logo: http://photos.prnewswire.com/prnh/20151104/283829LOGO ... to provide their customers enhanced security to access ...
(Date:4/19/2016)... 20, 2016 The new GEZE ... compact web-based "all-in-one" system solution for all door components. ... or the door interface with integration authorization management system, ... systems. The minimal dimensions of the access control and ... building installations offer considerable freedom of design with regard ...
(Date:4/15/2016)... 15, 2016 Research and ... Biometrics Market 2016-2020,"  report to their offering.  , ... , ,The global gait biometrics market is expected ... the period 2016-2020. Gait analysis generates ... be used to compute factors that are not ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... ... June 27, 2016 , ... ... innovative medical technologies, services and solutions to the healthcare market. The company's primary ... various distribution, manufacturing, sales and marketing strategies that are necessary to help companies ...
(Date:6/24/2016)... TOKYO , June 24, 2016  Regular discussions on ... to take place between the two entities said Poloz. ... in Ottawa , he pointed to the ... and the federal government. ... Poloz said, "Both institutions have common economic goals, why not ...
(Date:6/23/2016)... (PRWEB) , ... June 23, 2016 , ... ... the release of its second eBook, “Clinical Trials Patient Recruitment and Retention Tips.” ... and retention in this eBook by providing practical tips, tools, and strategies for ...
(Date:6/23/2016)... Md. , June 23, 2016 A person ... from the crime scene to track the criminal down. ... the U.S. Food and Drug Administration (FDA) uses DNA evidence ... Sound far-fetched? It,s not. The FDA ... sequencing to support investigations of foodborne illnesses. Put as simply ...
Breaking Biology Technology: