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

uke, Silverman and colleagues have been studying how a certain class of proteins called proteases, when uncontrolled, can kill cells. In the process, they discovered that another group of proteins, the serpins, might block, or inhibit, these destructive proteases and protect cells from injury. SRP-6 is among a vast family of pro-survival serpins, which are key regulatory molecules in many complex biologic processes, including blood cell coagulation, inflammation, tumor growth and cell death. Although previous research has shown that bloodstream serpins, including antithrombin and alpha-1 antitrypsin, control protein degradation, little is known about the role of serpins that function within cells, especially in a living organism.

Enter serendipity. When collecting specimens of a microscopic worm called Caenorhabditis elegans in water, rather than in a saline solution as is more common, Dr. Luke noticed that an extraordinarily large number of the animals were dying. My worm yield was way down, he said. When he examined the dying worms, he determined that they were genetic knock-outs that had been modified to be deficient in SRP-6. The normal worms were just fine.

A frequently studied animal model because of its 1,000-cell structure, transparency and easily visible development, C. elegans is a primitive organism whose complete genetic code has been sequenced and is well known to scientists. The worm typically lives in soil, flourishes in water and exists to eat bacteria and reproduce. The investigators were using a reverse genetic approach in which they hoped, by studying the relatively limited intracellular serpin repertoire of C. elegans, they could gain insights that might be applicable to serpin function in higher organisms, including humans.

Serpin proteins are critical, said Dr. Silverman, a neonatologist and a senior investigator at the Magee-Womens Research Institute. For example, we know that in patients who have a certain type o
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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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