Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Enzyme triggers cell death in heart attack

12.10.2012
Inhibiting CaMKII enzyme activity could lead to new therapies for heart disease

University of Iowa researchers have previously shown that an enzyme called CaM kinase II plays a pivotal role in the death of heart cells following a heart attack or other conditions that damage or stress heart muscle. Loss of beating heart cells is generally permanent and leads to heart failure, a serious, debilitating condition that affects 5.8 million people in the United States.

Now the UI team, led by Mark Anderson, M.D., Ph.D., professor and head of internal medicine at the UI Carver College of Medicine, has honed in on how CaM kinase II triggers heart cell death following heart damage, showing that the action takes place in the cells' energy-producing mitochondria. In animal tests, the team reports that blocking the enzyme can prevent heart cells from dying, and protects the animals from heart failure.

Mitochondrial are the cells' batteries, generating the energy cells need to work. In heart cells, energy produced by these small cellular components fuels each heartbeat. However, when the heart is stressed, for example during a heart attack, the mitochondria become leaky and non-functional, which triggers cell death and heart failure.

"We found that activity of the CaM kinase II enzyme in mitochondria promotes cell death when the heart is stressed," says Mei-ling Joiner, Ph.D., UI assistant professor of internal medicine and lead author of the study, which was published online Oct. 10 in the journal Nature. "The findings might help us advance treatment of heart diseases and reduce mortality after a heart attack."

The new study shows that activated CaM kinase II promotes leakiness of mitochondria and increases heart muscle damage by allowing too much calcium to enter mitochondria. Specifically, the UI team found that CaM kinase II regulates calcium entry into mitochondria by modifying a special mitochondrial calcium channel. Too much enzyme activity increased the amount of calcium flowing into mitochondria, and this calcium overload triggers cell death.

Using genetically modified mice, the team also showed that inhibiting CaM kinase II activity in mitochondria prevented the calcium overloading, reduced mitochondrial disruption, and protected the mice from heart cell death during heart attack.

These findings provide insight into molecular mechanisms for mitochondrial function and suggest that inhibiting the CaM kinase II enzyme in mitochondria could lead to new and more effective therapies for common forms of heart disease.

"Because mitochondria also play important roles in other diseases in brain and skeletal muscle, for example, our findings could also have broad implications for understanding and treating non-cardiac diseases," says Anderson, who also is director of the UI Cardiovascular Research Center.

In addition to Joiner and Anderson, the research team included UI researchers Olha Koval; Jingdong Li; B. Julie He; Chantal Allamargot; Zhan Gao; Elizabeth Luczak; Duane Hall; Brian Fink; Biyi Chen; Jinying Yang; Steven Moore; Thomas Scholz; Stefan Strack; William Sivitz; and Long-Sheng Song, and Peter Mohler at Ohio State University.

The research was funded in part by grants from the American Heart Association, the National Heart, Lung and Blood Institute, the Fondation Leducq for the Alliance for CaMKII Signaling, and Pew Scholars Trust.

Jennifer Brown | EurekAlert!
Further information:
http://www.uiowa.edu

More articles from Health and Medicine:

nachricht Biofilm discovery suggests new way to prevent dangerous infections
23.05.2017 | University of Texas at Austin

nachricht Another reason to exercise: Burning bone fat -- a key to better bone health
19.05.2017 | University of North Carolina Health Care

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

Im Focus: World's thinnest hologram paves path to new 3-D world

Nano-hologram paves way for integration of 3-D holography into everyday electronics

An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

How herpesviruses win the footrace against the immune system

26.05.2017 | Life Sciences

Water forms 'spine of hydration' around DNA, group finds

26.05.2017 | Life Sciences

First Juno science results supported by University of Leicester's Jupiter 'forecast'

26.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>