Working with mice, the Hopkins team found that the sudden oxygen bath triggered by restored blood flow causes cells to make a chemical so toxic it kills the cells. The work was published in two papers in the Proceedings of the National Academy of Sciences last week.
Although not sure why it happens, the Hopkins scientists believe the toxic chemical, PAR-polymer, acts like a molecular sledgehammer, or a death switch. "We've found evidence of it in cells following all types of injury," says Ted Dawson, M.D., Ph.D., the Leonard and Madlyn Abramson Professor of Neurodegenerative Diseases, professor of neurology and co-director of Hopkins' Neuroregeneration and Repair Program in the Institute of Cell Engineering (ICE).
The research team has named the cell death process caused by PAR-polymer "parthanatos," after Thanatos, the personification of death from Greek mythology.
To establish that PAR-polymer is indeed the culprit in the kind of reperfusion injuries long linked to heart attacks, strokes and a variety of blood vessel injuries, the researchers pumped mouse nerve cells full of PAR-polymer. The cells died, but to be sure PAR-polymer (and not something else) killed them, they examined the brains of mice engineered to lack an enzyme that chews up and gets rid of PAR. These mouse brains contained twice as much PAR-polymer as those of normal mice.
After the researchers induced a blood clot injury like a stroke, the same mice showed a 62 percent increase in the area of brain damage compared to normal littermates. Mice that contain more of the PAR-chewing enzyme suffered less brain damage than their normal littermates.
To figure out what triggers the death switch, the researchers tracked PAR-polymer's journey after cells made it. After 15 minutes, PAR-polymer hadn't gone anywhere. But after 30 to 60 minutes, the researchers discovered that much of it traveled right to areas where the switch normally resides.
The fate of the cell is irreversible once PAR-polymer sets off the trigger, says Valina Dawson, Ph.D., professor of neurology, co-director of the Neuroregeneration and Repair Program and author of the papers. "If we could figure out how to block PAR-polymer, we could design drugs that protect the switch and prevent cells from dying after heart attacks, stroke or other injuries," she says.
Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University
Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded after a glide flight with an Airbus A320 in ditching on the Hudson River. All 155 people on board were saved.
On January 15, 2009, Chesley B. Sullenberger was celebrated world-wide: after the two engines had failed due to bird strike, he and his flight crew succeeded...
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
27.02.2017 | Materials Sciences
27.02.2017 | Interdisciplinary Research
27.02.2017 | Life Sciences