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

l structures and even invading bacteria and viruses. But if the lysosome becomes damaged and leaky, these enzymes can turn against the cell and possibly overcome the serpin defense useful if the cell is part of a cancerous tumor.

The investigators determined that SRP-6 staves off necrosis by protecting the lysosome membrane from damage caused by the calpain family of cysteine proteases and by neutralizing other cysteine proteases released from injured cellular structures called organelles as they are being digested by the lysosome. As part of their study, Drs. Silverman, Luke and colleagues labeled enzymes within the lysosomes of SRP-6-deficient animals with a fluorescent biomarker to observe how these enzymes reacted after an injury to the critical structure.

The lysosomes popped, released their contents into the cell and these digestive enzymes began to activate, making the whole animal fluoresce, said Dr. Silverman. Again, this experiment showed the importance of SRP-6 in management of the necrosis pathway.

There are a lot of diseases associated with cell necrosis, such as stroke, neurodegenerative diseases and NEC, and now we know that the pathway to necrosis is much more systematic than we once thought it was, said Dr. Luke. With further study, we may be able to identify targets of intervention to halt the necrotic progression in some of these diseases and possibly even prevent them.


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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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