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Scorpion Venom Provides Clues to Cause, Treatment of Pancreatitis

A Brazilian scorpion has provided researchers at North Carolina State University and East Carolina University insight into venom’s effects on the ability of certain cells to release critical components. The findings may prove useful in understanding diseases like pancreatitis or in targeted drug delivery.

A common result of scorpion stings, pancreatitis is an inflammation of the pancreas. ECU microbiologist Dr. Paul Fletcher believed that scorpion venom might be used as a way to discover how pancreatitis occurs – to see which cellular processes are affected at the onset of the disease. Fletcher pinpointed a protein production system found in the pancreas that seemed to be targeted by the venom of the Brazilian scorpion Tityus serrulatus and then contacted NC State physicist Dr. Keith Weninger, who had studied that particular protein system.

“This particular protein system has special emphasis at two places in the body – the pancreas and the nervous system,” Weninger says. “In the pancreas, it is involved in the release of proteins through the membrane of a cell.”  The pancreas specializes in releasing two kinds of proteins using separate cells: digestive enzymes that go into the small intestine and insulin and its relatives that go into the bloodstream, yet this same release mechanism is important in all of our cells for many processes.

Cells move components in and out through a process called vesicle fusion. The vesicle is a tiny, bubble-like chamber inside the cell that contains the substance to be moved, stored and released – in this case, proteins like enzymes or hormones. The vesicle is moved through the cell and attaches to the exterior membrane, where the vesicle acts like an airlock in a spaceship, allowing the cell membrane to open and release the proteins without disturbing the rest of the cell’s contents. The proteins that aid in this process are known as Vesicle Associated Membrane Proteins, or VAMPs.

Weninger provided Fletcher with two different VAMP proteins found in the pancreas, VAMP2 and VAMP8. They were engineered to remove the membrane attachments so they could be more easily used for experiments outside cells and tissues. Fletcher’s team demonstrated that the scorpion venom attacked the VAMP proteins, cutting them in one place and eliminating the vesicle’s ability to transport its protein cargo out of the cell.

The results were published in the March 5 issue of the Journal of Biological Chemistry.

“We found that a particular enzyme in the scorpion’s venom removes a peptide, or small protein, that allows the vesicle to fuse with the cell membrane,” Fletcher says. “If you remove a pancreatic cell’s ability to absorb or release components, you end up with pancreatitis.”

“Viruses often exploit the same mechanism of vesicle fusion, but in reverse, in order to invade cells and replicate,” Weninger adds. “This work furthers our understanding of a basic cellular process and may lead to treatments for viruses and advances in treatments like chemotherapy, by allowing targeted drug delivery only to cancer cells.”

The Department of Physics is part of NC State University’s College of Physical and Mathematical Sciences.


Note to editors: An abstract of the paper follows.

“Vesicle-associated Membrane Protein (VAMP) Cleavage by a New Metalloprotease from the Brazilian Scorpion Tityus serrulatus*”
Authors: Paul L. Fletcher, Jr., Maryann D. Fletcher, East Carolina University; Keith Weninger, Trevor E. Anderson, North Carolina State University; and Brian M. Martin, National Institutes of Health
Published: March 5, 2010, in Journal of Biological Chemistry; VOL. 285, NO. 10, pp. 7405–7416

Abstract: We present evidence that venom from the Brazilian scorpion Tityus serrulatus and a purified fraction selectively cleave essential SNARE proteins within exocrine pancreatic tissue. Western blotting for vesicle-associated membrane protein type v-SNARE proteins (or synaptobrevins) reveals characteristic alterations to venom-treated excised pancreatic lobules in vitro. Immunocytochemistry by electron microscopy confirms both the SNARE identity as VAMP2 and the proteolysis of VAMP2 as a marked decrease in secondary antibody-conjugated colloidal gold particles that are predominantly associated with mature zymogen granules. Studies with recombinant SNARE proteins were used to determine the specific cleavage site in VAMP2 and the susceptibility of VAMP8 (endobrevin). The VAMP2 cleavage site is between the transmembrane anchor and the SNARE motif that assembles into the ternary SNARE complex. Inclusion of divalent chelating agents (EDTA) with fraction v, an otherwise active purified component from venom, eliminates SNARE proteolysis, suggesting the active protein is a metalloprotease. The unique cleavages of VAMP2 and VAMP8 may be linked to pancreatitis that develops following scorpion envenomation as both of these v-SNARE proteins are associated with zymogen granule membranes in pancreatic acinar cells. We have isolated antarease, a metalloprotease from fraction v that cleaves VAMP2, and report its amino acid sequence.

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  1. I have been stung by a scorpion on two separate occasions. The first time I was transported to UT medical Center in Knoxville Tennessee. Thank GOD,the ER doctor diagnosed me in minutes with acute pancreatitis due to a scorpion sting. He also informed me that if I had waited even15 minutes longer I would have died,in fact he gave me no guarantee that he could pull me out then. The pain made me wish I was home with Jesus. They knew how to treat me properly,they put me on a PCA pump of dilaudid,proper IV meds,after 12 days,I was discharged. The second time was about 2 weeks ago. After spending 6 hours waiting in the ER in Huntsville,another 7hrs in a treatment room,the doctors accused me of being an alcoholic,a street drug user,basically everything but the son of god. First off,I’m fighting 2 looking at possibly 3 types of cancer,I have been admitted to this hospital 39 times since 2011. THEY have performed 18 alleged emergency,life saving surgeries in that time. In 57 years,most recently the last 15 years I have never failed a drug screen. They know this,and still with held treatment until they confirmed this. Anyone who has had pancreatitis,and waits as I did till you are absolutely sure you have it,knows pain is beyond a shadow of a doubt,the absolute worst pain ever. Reflecting back on the difference in treatment is a ptsd trigger! Thank GOD for doctors that care and actually do their job! Please don’t cave in to our ever imploding medical system that has absolutely nothing to do with health care!

  2. My mom was diagnosed pancreatic cancer last October. She has been a DM patient for 15 years. Since last December, she presented with jaundice and heavily pruritus. After taking Vidatox, the pruritus became tolerable and not worsening, also she could have something to eat. But the discoloration of the skin and eyes is still on. Anyway, she is still live her normal life. I was very thankful for the scientist who found the way to control this disease so that my mom doesn’t have to do chemo-/radio-therapy which I guess will worsen her condition.