CONTACT: L. E. OHMAN
2130 Medical Laboratories
Iowa City IA 52242
(319) 335-6660; fax (319) 335-8034
Researchers further unravel the mystery of cell death
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.
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."