Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Enriched FAK Activity Protects Cardiomyocytes from Heart Attack Damage

By BiotechDaily International staff writers
Posted on 22 Mar 2012
Cardiovascular disease researchers have identified a protein in cardiomyocytes that when expressed at high levels protects heart cells from damage caused during myocardial infarction due to the sudden loss of oxygen.

Investigators at the University of North Carolina (Chapel Hill, USA) had shown previously that deletion of the enzyme focal adhesion kinase (FAK) exacerbated myocyte death following heart attack. FAK is a highly conserved, cytosolic, protein-tyrosine kinase involved in cell-cell and cell-matrix interaction and responsible for formation of the focal adhesion complex. It is widely expressed throughout development.

In the current study, the investigators examined the effect of enriched FAK activity on cardiomyocytes during and after heart attack (ischemia/perfusion) in a mouse model. To this end, they created a line of mice genetically engineered to express a highly active form of FAK (SuperFAK) in their cardiomyocytes.

They reported in the March 1, 2012, online edition of the journal Arteriosclerosis, Thrombosis and Vascular Biology that FAK activity in unstressed transgenic hearts was modestly elevated, but this had no discernible effect on anabolic heart growth or cardiac function. On the other hand, SuperFAK hearts exhibited a dramatic increase in FAK activity and a reduction in myocyte apoptosis and infarct size 24 to 72 hours following ischemia/perfusion.

Mechanistic studies revealed that elevated FAK activity protected cardiomyocytes from ischemia/perfusion-induced apoptosis by enhancing nuclear factor-kappaB (NF-kappaB)-dependent survival signaling during the early period of reperfusion (30 and 60 minutes). Moreover, adenoviral-mediated expression of SuperFAK in cultured cardiomyocytes attenuated H2O2 or hypoxia/reoxygenation-induced apoptosis. Blockade of the NF-kappaB pathway using a pharmacological inhibitor or small interfering RNAs completely abolished the beneficial effect of SuperFAK.

"This study shows that we can enhance existing cell survival pathways to protect heart cells during a heart attack," said senior author Dr. Joan Taylor, associate professor of pathology and laboratory medicine at the University of North Carolina. "We thought if we could activate FAK to a greater extent, then we could better protect those heart cells."

"I think folks could use this idea to exploit mutations in other molecules - by thinking about how to modify the protein so that it can be under natural controls," said Dr. Taylor. "Negative feedback loops are important because they "reset" the system."

Related Links:

University of North Carolina


Channels

Drug Discovery

view channel
Image: Star-like glial cells in red surround alpha-beta plaques in the cortex of a mouse with a model of Alzheimer\'s disease (Photo courtesy of Strittmatter laboratory/Yale University).

Experimental Cancer Drug Reverses Symptoms in Mouse Model of Alzheimer's Disease

An experimental, but clinically disappointing drug for treatment of cancer has been found to be extremely effective in reversing the symptoms of Alzheimer's disease (AD) in a mouse model.... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

NanoString and MD Anderson Collaborate on Development of Novel Multi-Omic Expression Profiling Assays for Cancer

The University of Texas MD Anderson Cancer Center (Houston, TX, USA) and NanoString Technologies, Inc. (Seattle, WA, USA) will partner on development of a revolutionary new type of assay—simultaneously profiling gene and protein expression, initially aiming to discover and validate biomarker signatures for immuno-oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.