Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PURITAN MEDICAL
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: A new micelle delivery system for the protective polyphenols resveratrol and quercetin (mRQ) may have value in cancer chemotherapy (Photo courtesy of Oregon State University).

Micelles Containing Resveratrol and Quercetin Reverse Doxorubicin Cardiotoxicity

Cancer researchers blocked the toxic effects of the cancer drug doxorubicin (DOX) by administering it together with the plant antioxidants resveratrol and quercetin. Although in use for more than 40... Read more

Lab Technologies

view channel
Image: The Leica DM2500 LED Microscope for clinical laboratories and research applications (Photo courtesy of Leica Microsystems).

New LED Microscope Completes Line of Clinical and Research Tools

A popular microscope used for both clinical and research applications is now available with LED illumination. The Leica (Wetzlar, Germany) DM2500 and DM2500 LED microscopes represent a class of tools... Read more

Business

view channel

Teva Buys Allergan Generic Business Unit

Teva Pharmaceutical Industries (Petah Tikva, Israel) has bought the Allergan (Irvine, CA, USA) generic drugs business for USD 40.5 billion in cash and stock, solidifying its position as the world's largest generic drug maker. Under the terms of the agreement, Teva will pay USD 33.75 billion in cash and USD 6.... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.