Scientists have discovered a protein that delays cell death, which could aid transplant survival and offer treatment for cancer, neurodegeneration and influenza.
Researchers from St Jude Children's Research Hospital in the US discovered how a set of proteins delays the 'executioner' machinery that kills damaged or infected cells in a process called necroptosis.
They knew that the 'executioner' in necroptosis was a protein called MLKL. When MLKL is activated by the necroptosis machinery, it triggers a piercing of the plasma membrane surrounding the cell, ultimately killing it.
Researchers showed that plasma membrane could repair itself by forming 'bubbles' of broken plasma membrane that would shed from the cell to repair the holes.
Proteins called ESCRT-III was responsible for forming the repair bubbles. The research also revealed that ESCRT-III delayed or prevented necroptosis by repairing breaks in the plasma membrane.
The delay gave the dying cells time to release signals to alert surrounding cells to the presence of a viral infection.
MLKL is not a point of no return for cell survival and that ESCRT-III could resuscitate damaged cells, researchers said.
In experiments relevant to transplantation, researchers measured levels of activated MLKL protein in tissue samples from kidneys used in transplants.
Such cells experience stress during the transplantations, and researchers suspected the cells would show signs of necroptosis, researchers said.
They found that although MLKL was activated in the kidney cells after transplantation, the cells did not die and this protection correlated with an increase in the levels of the ESCRT-III machinery necessary for rescue of cells with active MLKL.
Rescue treatments that prevent necroptosis in transplanted organs could reduce injury to the transplant caused by lack of oxygen, researchers said.
Drugs to rescue cells from necroptosis could also help prevent injuries to tissue deprived of blood by heart attack and stroke. In such cases, restoring blood flow and oxygenation triggers inflammation that kills tissue.
Cell-rescuing drugs could also thwart cancer spread by protecting blood vessel cells from being killed by tumour cells, said Douglas Green from St Jude Children's Research Hospital.
Tumour cells escape the bloodstream to spread in the body by killing blood vessels. Blocking the rescue machinery might also prove useful in treating cancers, by enhancing death of cancer cells by necroptosis, he said.
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