Researchers at Ben Gurion University of the Negev and Soroka University Medical Center explore the uses of a molecule called humanin to halt necrosis – stopping cell death in its tracks
Strokes, heart attacks and traumatic brain injuries are separate diseases with certain shared pathologies that achieve a common end – cell death and human injury due to hypoxia, or lack of oxygen. In these diseases, a lack of blood supply to affected tissues begins a signaling pathway that ultimately halts the production of energy-releasing ATP molecules – a death sentence for most cells.
AGA(C8R)-HNG17 and the mitochondrial tracker tetramethylrhodamine methyl ester in PC-12 cells (rat pheochromocytoma, of neuronal origin) 10 min after inducing necrosis by cyanide, exhbiting co-localization of humanin and mito-tracker at the mitochondria. Both trackers are co-localized where their lifetime is the longest.
By employing derivatives of humanin, a naturally occurring peptide encoded in the genome of cellular mitochondria, researchers at Ben Gurion University of the Negev are working to interrupt this process, buying precious time for tissues whose cellular mechanisms have called it quits.
"The present findings could provide a new lead compound for the development of drug therapies for necrosis-related diseases such as traumatic brain injury, stroke and myocardial infarction - conditions for which no effective drug-based treatments are currently available [that work by blocking necrosis]," said Abraham Parola, a professor of biophysical chemistry at Ben Gurion University of the Negev in Beer-Sheva, Israel. Parola is presently a visiting professor of Biophysical Chemistry & Director of Natural Sciences at New York University Shanghai, and will speak about his lab's finding's this week at the Biophysical Society's 59th annual meeting in Baltimore, Md.
The humanin derivatives work by counteracting the decrease in ATP levels caused by necrosis. The researchers tested the effectiveness of the humanin analogues AGA(C8R)-HNG17 and AGA-HNG by treating neuronal cells with these peptides prior to exposure to a necrotic agent. The experiments were a success.
Parola's previous work has dealt with membrane dynamics and the mechanism of action of anti-angiogenesis drugs, which cause starvation of malignant tumor growths by preventing the supply of nutrients and oxygen to the fast growing tissue, in addition to various other biophysical and molecular medicine and diagnostic topics.
"A recent paper published by our group suggested the involvement of cardiolipin [a phospholipid in inner mitochondrial membranes] in the necrotic process," Parola said. "During this work we stumbled along humanin and were intrigued by its anti-apoptotic effect, and extended it to anti-necrotic effect."
Parola and his colleagues also performed in vivo studies by treating mice that had had traumatic brain injuries with an HNG17 analogue, which successfully reduced cranial fluid buildup and lowered the mice's neuronal severity scores, a metric in which a higher number corresponds with greater degrees of neurological motor impairment.
As the peptides Parola and his colleagues used are derivatives of naturally occurring humanin, an ideal treatment might involve a drug delivery system with the HNG17 as the lead compound, a process aided by the ability of the peptides to penetrate the cell membrane without the use of additional reagents.
Future work for Parola and his colleagues includes further exploration of ischemic activity in liver cirrhosis, as induced by acetaminophen activity, in addition to searching for a synergistic effect between humanin and other anti-necrotic agents, such as protease inhibitors, to increase its clinical potential.
The presentation, "The mechanism of inhibition of necrosis by humanin derivatives: a potential treatment for ischemia and related diseases" by by Aviv Cohen, Jenny Lerner-Yardeni, David Meridor, Moreno Zamai, Valeria R. Caiolfa, Roni Kasher, Ilana Nathan and Abraham H. Parola is at 1:45 PM, on Sunday, Feb. 8, 2015, at the Baltimore Convention Center, in Hall C, poster 766. ABSTRACT: http://bit.ly/1y47YVX
ABOUT THE MEETING
Each year, the Biophysical Society Annual Meeting brings together more than 6,500 researchers working in the multidisciplinary fields representing biophysics. With more than 3,600 poster presentations, over 200 exhibits, and more than 20 symposia, the BPS Annual Meeting is the largest meeting of biophysicists in the world. Despite its size, the meeting retains its small-meeting flavor through its subgroup symposia, platform sessions, social activities and committee programs. The 59th Annual Meeting will be held at the Baltimore Convention Center.
The Biophysical Society invites professional journalists, freelance science writers and public information officers to attend its Annual Meeting free of charge. For press registration, contact Ellen Weiss at or Jason Bardi at 240-535-4954.
ABOUT THE SOCIETY
The Biophysical Society, founded in 1958, is a professional, scientific Society established to encourage development and dissemination of knowledge in biophysics. The Society promotes growth in this expanding field through its annual meeting, bi-monthly journal, and committee and outreach activities. Its 9,000 members are located throughout the U.S. and the world, where they teach and conduct research in colleges, universities, laboratories, government agencies, and industry. For more information on the Society, or the 2015 Annual Meeting, visit http://www.biophysics.org
Jason Socrates Bardi, AIP
Jason Socrates Bardi, AIP | newswise
Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications
Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine