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Pathway to cell death redefined in landmark study
Date:9/21/2007

PITTSBURGH, Sept. 20 -- A new study led by investigators from the University of Pittsburgh School of Medicine demonstrates that the process of necrosis, long thought to be a chaotic, irreversible pathway to cell death, may actually be triggered as part of a regulated response to stress by a powerful protein, SRP-6, that can potentially halt necrosis in its path. Further, the research team realized that this protein might be harnessed to direct some cells -- those in cancerous tumors, for instance -- to die, while saving others, such as degenerating neural cells responsible for Alzheimers and Parkinsons diseases. The work appears on the Sept. 21 cover of the journal Cell.

This remarkable molecular trigger, SRP-6, is a serine protease inhibitor or serpin, and targets the cells digestive center, the lysosome. The authors report that the family of intracellular serpins may help cells survive in the face of stressors by protecting against lysosomal injury and its cellular consequences.

For years, we believed that cell death related to a catastrophic insult such as a stroke or heart attack that deprives tissue of oxygen couldnt really be treated, so we focused on strategies to prevent further damage by restoring blood flow as quickly as possible with clot busters and surgery, said Gary A. Silverman, M.D., Ph.D., chief of newborn medicine in the department of pediatrics at the Pitt School of Medicine and the studys senior author. But our research indicates that necrosis can be interrupted and possibly repaired, even after the injury process is well underway. This insight has exciting implications for the management of heart disease, stroke and neurological illnesses.

Representing more than five years of study, the Cell publication is the result of a chance observation made by primary author Cliff J. Luke, Ph.D., assistant professor of pediatrics at Pitt and an investigator at the university-affiliated Magee-Womens Research Institute. Drs. L
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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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