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:12/2/2016)... December 1, 2016 The ... Voice), Future Technology (Iris Recognition System), Vehicle Type ... Global Forecast to 2021", published by MarketsandMarkets, the ... in 2016, and is projected to grow to ... of 14.06%.      (Logo: http://photos.prnewswire.com/prnh/20160303/792302) ...
(Date:11/30/2016)... CHICAGO , Nov. 30, 2016  higi ... a new partnership initiative targeting national brands, industry ... and reward their respective audiences for taking steps ... Since its inception in 2012, higi has built ... US, impacting over 38 million people who have ...
(Date:11/29/2016)... Nearly one billion matches per second with DERMALOG,s high-speed AFIS    ... ... DERMALOG is Germany's largest Multi-Biometric supplier: The company's Fingerprint ... ... Multi-Biometric supplier: The company's Fingerprint Identification System is part of an efficient ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... ... December 08, 2016 , ... Opal ... provide essential device-to-computer interconnect using USB or PCI Express, announced the FOMD-ACV-A4, the ... FOMD-ACV-A4 is a small, thin, SODIMM-style module that fits a standard 204-pin SODIMM ...
(Date:12/8/2016)... 2016  Anaconda BioMed S.L., a pre-clinical stage medical ... generation neuro-thrombectomy system for the treatment of Acute Ischemic ... MD to join its Scientific Advisory Board (SAB). The ... of scientific and clinical experts to Anaconda BioMed S.L., ... BRAIN ® to its clinical phase. The SAB ...
(Date:12/8/2016)... ... December 08, 2016 , ... Microbial genomics leader, uBiome, joins ... one of just six company finalists in the Health & Medicine category. Over ... nominated as finalists in this year’s awards include Google, SpaceX, Oculus, and SolarCity. ...
(Date:12/8/2016)... , Dec. 8, 2016 Soligenix, Inc. (OTCQB: ... focused on developing and commercializing products to treat rare ... today that it will be hosting an Investor Webcast ... on the origins of innate defense regulators (IDRs) as ... of oral mucositis and the recently announced and published ...
Breaking Biology Technology: