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
Cholesterol-lowering drugs may fight infectious disease
22.08.2017 | Duke University
Once invincible superbug squashed by 'superteam' of antibiotics
22.08.2017 | University at Buffalo
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
23.08.2017 | Life Sciences
23.08.2017 | Life Sciences
23.08.2017 | Physics and Astronomy