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Embargoed for release December 17, 1997
Programmed Cell Death
Search accelerates for mechanism underlying cancer, stroke, heart attack
Sometimes cells are supposed to die. The process is called apoptosis or programmed cell death. Cells die as a part of normal development, as some of them specialize and differentiate into organs and systems. They die in self-defense when they are infected by intruders such as bacteria and viruses. And sometimes they die because their normal life cycle is disrupted by chemicals or other toxins.
Other times cells don't die when they are supposed to. Something interferes with the normal process of apoptosis, and cells continue growing and reproducing out of control. The result of this breakdown of apoptosis is cancer.
Pathologists at the University of Maryland School of Medicine now have made a giant stride toward mapping the tortuous biochemical pathway of programmed cell death. Once the complex interaction of mechanisms along the pathway to programmed cell death is unraveled, it should be possible to devise drugs to cause cell death when it is needed, as in cancer, and to prevent it in conditions such as stroke and heart attack.
By micro-injecting cytochrome cña protein normally found in the mitochondria or energy-generating structures within cellsñBenjamin F. Trump, MD, and colleagues have speeded up enormously the process of programmed cell death in normal rat kidney cells.
They will present their findings at the American Society for Cell Biology annual meeting at the Washington Convention Center in Washington, DC, at noon Wednesday, December 17, 1997.
Within 30 minutes after cytochrome c was injected directly into the cytoplasm inside the cells, the cells began to show typical changes in structure that indicate that apoptosis was under way. By five hours after the injection, 50 to 60 percent of the cells had died.
Earlier experiments involving injection of P53, another normal cellular protein that causes cell death at appropriate times, showed similar results but took 18 to 48 hours.
"This has moved us way down the pathway, close to the end," said Trump, professor and chairman of pathology at the Baltimore-based medical school. "By simply micro-injecting cytochrome c, we can reproduce the other steps in the process and do it incredibly quickly. Now we want to know the role of other proteins along the pathway, such as the proteases and bcl2, and whether an influx of calcium finally causes the mitochondria to swell, the cell membrane to swell, and the cell to die."
Trump's lab has pioneered in cell-death research.
His colleagues on the cytochrome-c research are Seung H. Chang, Patricia C. Phelps, M.L. Ebersberger and Irene K. Berezesky, all in the University of Maryland School of Medicine Department of Pathology.
The work was funded by the National Institutes of Health.
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