Compound developed by scientists protects heart cells during and after attack

February 7, 2013

Using two different compounds they developed, scientists from the Florida campus of The Scripps Research Institute (TSRI) have been able to show in animal models that inhibiting a specific enzyme protects heart cells and surrounding tissue against serious damage from heart attacks. The compounds also protect against additional injury from restored blood flow after an attack, a process known as reperfusion.

The study, which was led by Philip LoGrasso, a professor and senior scientific director of discovery biology at Scripps Florida, appears in the February 8, 2013 print edition of The .

A heart attack severely restricts blood supply, starving heart cells and surrounding tissue of oxygen, which can cause enormous damage in relatively little time—sometimes in just a few minutes. Known as an ischemic cascade, this drop-off of oxygen results in a sudden crush of metabolic waste that damages cell membranes as well as the mitochondria, a part of the cell that generates chemical energy and is involved in cell growth and death.

Unfortunately, restoring blood flow adds significantly to the damage, a serious medical issue when it comes to treating major ischemic events such as heart attack and stroke. Reperfusion re-invigorates production of and reactive that attack and , exacerbating inflammation, turning loose to attack otherwise salvageable cells and maybe even inducing potentially fatal .

The new study found that inhibiting the enzyme, c-jun-N-terminal kinase (JNK), pronounced "junk," protected against ischemic/reperfusion injury in rats, reducing the total volume of tissue death by as much as 34 percent. It also significantly reduced levels of reactive oxygen species and mitochondrial dysfunction.

In earlier studies, TSRI scientists found that JNK migrates to the mitochondria upon oxidative stress. That migration, coupled with JNK activation, they found, is associated with a number of serious health issues, including liver damage, neuronal cell death, stroke and heart attack. The peptide and small molecule inhibitor (SR3306) developed by LoGrasso and his colleagues blocks those harmful effects, thereby reducing programmed cell death four-fold.

"This is the same story," said LoGrasso. "These just happen to be heart cells, but we know that oxidative stress kills cells, and JNK inhibition protects against this stress. Blocking the translocation of JNK to the mitochondria is essential for stopping this killing cascade and may be an effective treatment for damage done to during an ischemic/reperfusion event."

In addition, LoGrasso said, biomarkers that rise during a heart attack shrink in the presence of JNK inhibition, a clear indication that blocking JNK reduces the severity of the infarction.

Explore further: Scientists uncover potential drug target to block cell death in Parkinson's disease

More information: "Inhibition of JNK Mitochondrial Localization and Signaling is Protective Against Ischemia-Reperfusion Injury in Rats," www.jbc.org/content/early/2012 … M112.406777.full.pdf

Related Stories

Scientists uncover potential drug target to block cell death in Parkinson's disease

January 10, 2013
Oxidative stress is a primary villain in a host of diseases that range from cancer and heart failure to Alzheimer's disease, Amyotrophic Lateral Sclerosis and Parkinson's disease. Now, scientists from the Florida campus of ...

Study shows man-made fat may limit damage to heart attack victims

August 5, 2011
A man-made fat called Intralipid, which is currently used as a component of intravenous nutrition and to treat rare overdoses of local anesthetics, may also offer protection for patients suffering from heart attacks.

Key protein interactions involved in neurodegenerative disease revealed

November 8, 2012
Scientists from the Florida campus of The Scripps Research Institute (TSRI) have defined the molecular structure of an enzyme as it interacts with several proteins involved in outcomes that can influence neurodegenerative ...

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

October 11, 2012
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 ...

Recommended for you

Could aggressive blood pressure treatments lead to kidney damage?

July 18, 2017
Aggressive combination treatments for high blood pressure that are intended to protect the kidneys may actually be damaging the organs, new research from the University of Virginia School of Medicine suggests.

Quantifying effectiveness of treatment for irregular heartbeat

July 17, 2017
In a small proof-of-concept study, researchers at Johns Hopkins report a complex mathematical method to measure electrical communications within the heart can successfully predict the effectiveness of catheter ablation, the ...

Concerns over side effects of statins stopping stroke survivors taking medication

July 17, 2017
Negative media coverage of the side effects associated with taking statins, and patients' own experiences of taking the drugs, are among the reasons cited by stroke survivors and their carers for stopping taking potentially ...

Study discovers anticoagulant drugs are being prescribed against safety advice

July 17, 2017
A study by researchers at the University of Birmingham has shown that GPs are prescribing anticoagulants to patients with an irregular heartbeat against official safety advice.

Protein may protect against heart attack

July 14, 2017
DDK3 could be used as a new therapy to stop the build-up of fatty material inside the arteries

Heart study finds faulty link between biomarkers and clinical outcomes

July 14, 2017
Surrogate endpoints (biomarkers), which are routinely used in clinical research to test new drugs, should not be trusted as the ultimate measure to approve new health interventions in cardiovascular medicine, according to ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.