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- IOWA CITY, Iowa - Cells die. It's a normal part of development and of aging.
Cell death also plays a role in many deadly diseases such as cancer, stroke
and Alzheimer's disease. The more scientists understand about the process
of cell death, the better able they will be to combat those and other diseases.
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- 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.
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- 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.
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- 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.
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- 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.
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- 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.
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- "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."
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