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Jekyll and Hyde: Cells' executioner can also stave off death
Date:3/3/2011

In addition, several experimental anti-cancer and anti-inflammatory drugs aim to alter caspase 8 levels in order to induce death in cancer cells or reduce inflammation.

"Until recently, scientists viewed programmed cell death mainly as apoptosis, a program of self-destruction deliberately set in motion through signals cells receive from outside," Mocarski says.

For example, apoptosis ensures that white blood cells responding to an infection don't multiply indefinitely. White blood cells have built-on triggers on their surfaces that activate caspase 8, which unleashes a cascade of enzymes that break down the contents of the cell.

In contrast to apoptosis, necrosis was seen as unregulated death by neglect, until the discovery of an alternative form of cell death, driven by RIP3, called programmed necrosis. This looks like necrosis under the microscope, but like apoptosis is orchestrated by the cell from within rather than occurring because of injury or infection. Mocarski's group recently showed that RIP3 enables cells to sabotage themselves if they are infected by a virus, an activity where apoptosis was once thought to be the most important.

"For several years, the puzzle was: what are the non-apoptotic functions of caspase 8, since there are numerous systems that are impacted by not having it," Mocarski says. "Now we have to consider that the absence of caspase 8 is actually revealing death by RIP3."

Mice lacking both caspase 8 and RIP3 have blood vessels and blood cells that look healthy. However, a few months after birth, they develop swollen lymph nodes, because their white blood cells do not go through apoptosis normally. Other scientists have shown that mice that have caspase 8 missing only in the skin have chronic skin inflammation, a condition resembling eczema in humans.

"Our results indicate that whatever caspase 8 was doing in the skin, removing RIP3 takes care of it," Mocarski says.


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Contact: Joe Quimby
joseph.quimby@emory.edu
404-727-3366
Emory University
Source:Eurekalert

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