The study, in which mice were bred to make a supercharged version of the protein focal adhesion kinase, or FAK, appeared March 1 in the online edition of the journal Arteriosclerosis, Thrombosis and Vascular Biology.
Following heart attack, heart cells are stressed due to lack of oxygen. When SuperFAK (in green) is expressed in the heart, it is further activated and protects heart cells from oxidative stress (in red). Credit: Joan Taylor, Ph.D
"This study shows that we can enhance existing cell survival pathways to protect heart cells during a heart attack," said Joan Taylor, PhD, associate professor in UNC's department of pathology and laboratory medicine. Taylor added that the findings could lead to new treatment approaches for heart attacks and may have broad implications for scientists seeking to manipulate the body's natural defensive systems.
During a heart attack, oxygen-deprived heart cells emit signals that activate the usually inert protein FAK, like the cry of a damsel in distress awakening her sleeping knight. If the gallant FAK arrives in time, it can save the cell and reduce permanent damage to the heart.
Taylor and her colleagues were intrigued by FAK's protective abilities. "We thought if we could activate FAK to a greater extent, then we could better protect those heart cells," said Taylor. Based on their previous studies that defined the signals induced by FAK in heart cells, they reasoned that expression of FAK set to an "always-on" position would eventually suffer uncontrolled inflammation and heart failure. "Simply having more of a good thing isn't always better," said Taylor. "The dynamics of the protein's activities are important to appropriately transmitting those survival signals."
The researchers then adjusted their formula to create a new protein they called "SuperFAK." To enhance its protective abilities without the harmful side effects, SuperFAK was primed for activation—ready to rush to the scene at the slightest provocation from stressed heart cells—but remained under the control of the mice's natural feedback systems that would shut it off when the crisis passed.
Mice with SuperFAK showed a much stronger FAK response during a heart attack than mice with the natural protein, and three days later had about 50 percent less heart damage. Critically, SuperFAK deactivated at the appropriate time, so the eight-week follow-up revealed no detrimental effects.
The findings offer evidence that, rather than simply activating or de-activating key proteins, researchers can benefit from a more nuanced approach that taps into the body's natural feedback loops. "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 Taylor. "Negative feedback loops are important because they 'reset' the system."
The findings also may help researchers augment FAK in patients undergoing chemotherapy. Some chemotherapy drugs are known to break down FAK, leaving patients' hearts more vulnerable to damage.
Co-authors included Zhaokang Cheng, Laura A. DiMichele, Zeenat S. Hakim, Mauricio Rojas and Christopher P. Mack. The research was supported by grants from the National Institutes of Health and the American Heart Association.
Les Lang | EurekAlert!
Newly designed molecule binds nitrogen
23.02.2018 | Julius-Maximilians-Universität Würzburg
Atomic Design by Water
23.02.2018 | Max-Planck-Institut für Eisenforschung GmbH
A newly developed laser technology has enabled physicists in the Laboratory for Attosecond Physics (jointly run by LMU Munich and the Max Planck Institute of Quantum Optics) to generate attosecond bursts of high-energy photons of unprecedented intensity. This has made it possible to observe the interaction of multiple photons in a single such pulse with electrons in the inner orbital shell of an atom.
In order to observe the ultrafast electron motion in the inner shells of atoms with short light pulses, the pulses must not only be ultrashort, but very...
A group of researchers led by Andrea Cavalleri at the Max Planck Institute for Structure and Dynamics of Matter (MPSD) in Hamburg has demonstrated a new method enabling precise measurements of the interatomic forces that hold crystalline solids together. The paper Probing the Interatomic Potential of Solids by Strong-Field Nonlinear Phononics, published online in Nature, explains how a terahertz-frequency laser pulse can drive very large deformations of the crystal.
By measuring the highly unusual atomic trajectories under extreme electromagnetic transients, the MPSD group could reconstruct how rigid the atomic bonds are...
Quantum computers may one day solve algorithmic problems which even the biggest supercomputers today can’t manage. But how do you test a quantum computer to...
For the first time, a team of researchers at the Max-Planck Institute (MPI) for Polymer Research in Mainz, Germany, has succeeded in making an integrated circuit (IC) from just a monolayer of a semiconducting polymer via a bottom-up, self-assembly approach.
In the self-assembly process, the semiconducting polymer arranges itself into an ordered monolayer in a transistor. The transistors are binary switches used...
Breakthrough provides a new concept of the design of molecular motors, sensors and electricity generators at nanoscale
Researchers from the Institute of Organic Chemistry and Biochemistry of the CAS (IOCB Prague), Institute of Physics of the CAS (IP CAS) and Palacký University...
15.02.2018 | Event News
13.02.2018 | Event News
12.02.2018 | Event News
23.02.2018 | Physics and Astronomy
23.02.2018 | Health and Medicine
23.02.2018 | Physics and Astronomy