A well-known molecule of polyphosphate, a natural polymer, was shown to speed blood clot formation as well as clot stabilization. Promising research from groups from the University of Illinois at Urbana-Champaign and the University of Georgia was published in the Proceedings of the National Academy of Sciences (PNAS):
Polyphosphate was shown to have three important roles, said James H. Morrissey, a biochemist in the U. of I. College of Medicine at Urbana-Champaign. The inorganic compound accelerates two parts of the coagulation cascade – the contact-activation pathway and factor V, a protein that forms thrombin – leading to fibrin and clots. Finally, he said, polyphosphate delays the breakdown of clots, which causes renewed bleeding.
The PNAS report comes about a year after former Illinois scientist Roberto Docampo, now a professor of cellular biology at Georgia’s Center for Tropical and Emerging Global Diseases, documented in the Journal of Biological Chemistry (Oct. 22, 2004) that dense granules in human platelets contain polyphosphate.
In the early 1990s, Docampo determined that a tiny granule, a subcellular pouch, in yeast, fungi and bacteria – long thought to be for storage – was a fully operational organelle. It contained pyrophosphatase, a pump-like enzyme that allows proton transport. He named it the acidocalcisome for its acidic and calcium components.
Docampo has since found virtually identical pyrophosphate-containing pouches in numerous prokaryotic organisms, challenging the theory on the origin of eukaryotic organelles and suggesting a targeted approach to killing many disease-causing organisms.
“Because I saw electron microscopy pictures of the blood platelets’ dense granules taken many years ago that were almost identical to the pictures we took of the acidocalcisomes of different protozoa,” he said, “I thought it would be a good idea to test if they were similar in other aspects. When we found that polyphosphate was released from platelets upon stimulation, I immediately thought about a potential role in coagulation.”
In collaboration with Morrissey, an expert on blood clotting, Docampo and a team of U. of I. graduate and postdoctoral students tested the effect of adding polyphosphate to platelet-poor plasma in a series of in-vitro experiments to see if it enhanced blood clotting. The results were dramatic, Morrissey said, adding that the presence of polyphosphate may help explain how platelets accelerate the process of blood clotting.
Polyphosphate is in every living organism, but scientists thought it to be a molecular fossil conserved from prebiotic time. “This is something that has mainly been studied in bacteria,” Docampo said. “There is almost no data on polyphosphates in vertebrates, including humans. No role was seen for them, so there was little interest in studying them.”
The Center for Hemostasis Research will carry the new discovery further. Morrissey and Illinois colleagues Stephen Sligar, a professor of biochemistry, and Lawrence B. Schook, a professor of animal sciences, will lead a variety of experiments. Among them, they will test the use of polyphosphate as an additive to topical agents as well as new nanotechnologies in an animal model to develop effective treatments for situations involving uncontrollable bleeding.
Such scenarios, Morrissey said, could include treatment for wounds sustained on battlefields or in accidents, or for hemophilia and other diseases with coagulation deficits.
“The big picture is that we’ve found a new function for an ancient molecule,” he said.
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