Monday, April 19, 2010

Breaking Down Pancreatitis

Jim Allen

The Pancreas is that underappreciated organ beneath your stomach which nobody pays attention to until it swells to the size of a foot-long sub and jams into your nearby internal organs. This swelling, commonly known as acute Pancreatitis, has many causes including the introduction of scorpion venom into an animal’s body. Researchers Keith Weninger of North Carolina State’s Department of Physics and Paul Fletcher of East Carolina University’s Department of Microbiology and Immunology have recently completed a study of the effects of scorpion venom on protein and enzyme production in the pancreas of guinea pigs. According to the researchers, “Clinical studies report that scorpion venoms induce significant pathology, including acute pancreatitis in humans following envenomation.” Approximately 80,000 people are affected by acute pancreatitis every year in the U.S, a number which could be significantly reduced using data collected by Weninger and his team.

It is important to note that while scorpion stings are widespread in the U.S., stings do occur worldwide especially in Africa and India. Additionally, according to the researchers, “Secretagogues of non-scorpion venom origin used by others can also produce similar effects but require excessive levels of administration in vivo in order to achieve those results”.

In their experiments, swelling of the pancreas was caused by a toxin-induced failure of the normal vesicular traffic, which is the basis for intra-cellular transport of proteins. Toxin molecules attacked modified proteins referred to as vesicle-associated membrane proteins (VAMPs), rendering them unable to transport other proteins throughout the pancreas. Basically, pancreatitis was onset by disabling the pancreatic cells ability to release or absorb components.

This transport process is called “vesicle fusion” and it works like so. The contents of one cell may be mixed or injected into another cell or VAMP that can be transferred to another location. Weninger and Fletcher report that “understanding of these functions is fundamental to extending knowledge of transport in normal and diseased cells.” Additionally, “Simultaneous cleavage of multiple SNAREs, such as VAMP2, VAMP3, and VAMP8, would presumably have major physiological consequences”.

A cutting of protein molecules, known as proteolysis, occurred between the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) motif and the transmembrane anchor. This cleavage was reportedly performed by an enzyme called antarease, a newly discovered “Metalloprotease”, which was not previously present in amino acid sequencing databases.

Before their experiments, no scorpion toxins had been associated with intracellular targets. Therefore, “a definitive function in pathogenesis for the metalloprotease activity of scorpion venom remains to be determined beyond a theoretical role”.

According to Dr. Weninger, “results from the experiments have important implications for potential effects on secretory discharge as well as vesicular transport mechanisms in the exocrine process.” Understanding the effects of VAMP cleavage by a metalloprotease will lead to a better understanding of the mechanisms responsible for pancreatitis and potential treatments or cures. Vesicle fusion has been explored in recent years as a method of cellular-level drug introduction.

Results of the experiment were published in the March edition of the Journal of Biological Chemistry.

Fletcher Jr., Paul L. et al "Vesicle-associated Membrane Protein (VAMP) Cleavage By a New Metalloprotease from the Brazilian Scorpion Tityus Serrulatus*." Journal of Biological Chemistry 285.10 (2010): 7405-7416. Web. 06 Apr. 2010. .

1 comment:

  1. I LOVE YOUR FIRST SENTENCE. Love, love, love. I'm drawing a little heart in the air with my two pointer fingers.

    Graph 3: too much technical terminology. "Vesicular traffic" needs to become "traffic in the blood vessels and spongey tissues" or some such...

    I really like the way you link to the vesicular fusion def--"like so." Very nice.