Researchers Further Unravel The Mystery Of Cell Death

Scientists know that badly damaged cells that cannot be repaired are slated for programmed cell death known as apotosis. They also know that in the fruit fly proteins called Reaper, Grim and Hid appear prior to cell death, but until now, they did not understand their role in apotosis. Toshinori Hoshi, Ph.D., UI associate professor of physiology and biophysics, and colleagues at the Beckman Research Institute of the City of Hope, discovered that these proteins cause over-stimulation of cells, leading to death. The findings are published in the Sept. 29 issue of the journal Proceedings of the National Academy of Sciences.

Cells become active when they communicate with each other through a complex "telephone" system where one cell sends an activation message or impulse to the next, and that cell activates the next and so on. The impulses that activate each cell usually arise from a chemical message, or neurotransmitter.

Most cells in the body are relatively passive or quiescent until an impulse excites them to action, but once they have acted they need to return to the quiet state or die from over excitation. Studying the protein Reaper, Hoshi and colleagues found that it doesn't allow the cell to return to the nonactive state, thus exciting itself to death.

When a quiescent cell receives chemical messages spurring it into action, ions such as sodium or calcium rush inside the cell. After the message is sent, the cell is ready to return to the quiescent state. To do so, potassium leaves the cell through special potassium channels. Hoshi found that Reaper inserts part of its structure into the pore-like channel, thus clogging the pore and blocking the release of potassium, preventing the cell from returning to its resting state. The researchers also found that a mutated Reaper protein that is not able to jam the potassium channel, did not cause apotosis.

It is not clear why these proteins appear in certain cells, Hoshi said. It may be the result of stress produced by a heart attack or stroke, or even the food we eat. But understanding the process by which they initiate cell death has enormous implications.

"If there isn't enough protein like Reaper to initiate cell death, abnormal cells, like cancer cells, are not destroyed. If there is too much, it causes neurodegeneration, or kills cells that shouldn't die," Hoshi said. "We think mechanisms like this exist in humans too," Hoshi added, "and we are now working with mammalian cells in culture."