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Pathway to cell death redefined in landmark study
Date:9/20/2007

f skin cancer, those whose tumors express a lot of intracellular serpins dont do as well. Now we know that SRP-6 is a crucial pro-survival mechanism that can protect cells from injury, initiate repair after injury, or, if absent, lead to a cascade of cell death.

With further investigation, it may be possible to use this knowledge to deprive cancer cells of their serpin protectors and target them for death. Alternatively, physicians might be able to boost serpin activity to stop cells from dying for example, intestinal cells affected by the bacterial infection necrotizing enterocolitis (NEC), a major cause of death and illness in fragile, premature infants.

We still treat NEC the same way we did 30 years ago, with supportive care, antibiotics and surgery to remove dead portions of intestine, said Dr. Silverman. We cant stop the mucosal lining from dying. But with these worms as models, we can do drug screens to search for compounds that can block necrosis.

Drs. Silverman, Luke and colleagues have dramatically illustrated the devastating consequences of cellular stress in C. elegans when the crucial protector SRP-6 is missing. A cascade of cell necrosis begins in SRP-6-deficient animals exposed to a number of different stressors, including water, heat and lack of oxygen. In the case of water exposure, the SRP-6 knock-outs move a bit but soon become immobile. Finally, the worms organs are violently expelled through their bodily openings, resulting in what the authors refer to as a grim fate.

Animals with normal genetic sequences are fine in water, but the knock-out animals usually die rapidly, said Dr. Luke, explaining that this observation led him to realize the importance of SRP-6 in protecting the lysosome, an internal cell structure enclosed in its own protective membrane that acts as the cells garbage disposal. Powerful enzymes within the lysosome digest old, worn out proteins, carbohydrates, lipids, DNA, RNA, other damaged cel
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Contact: Michele Baum
BaumMD@upmc.edu
412-647-3555
University of Pittsburgh Schools of the Health Sciences
Source:Eurekalert

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