Prion protein fragment (106-126) induces prothrombotic state by raising platelet intracellular calcium and microparticle release

Cell Calcium
Ram L MallickDebabrata Dash

Abstract

Prion diseases are neurodegenerative disorders where infectious prion proteins (PrP) accumulate in brain leading to aggregation of amyloid fibrils and neuronal cell death. The amino acid sequence 106-126 from prion proteins, PrP(106-126), is highly amyloidogenic and implicated in prion-induced pathologies. As PrP is known to be expressed in blood following leakage from brain tissue, we sought to investigate its biological effects on human platelets, which have been widely employed as 'peripheral' model for neurons. Our findings suggested that, PrP(106-126) (20μM) induced dramatic 30-fold rise in intracellular calcium (from 105±30 to 3425±525nM) in platelets, which was attributable to influx from extracellular fluid with comparatively less contribution from intracellular stores. Calcium mobilization was associated with 8-10-fold stimulation in the activity of thiol protease calpain that led to partial cleavage of cytoskeleton-associated protein talin and extensive shedding of microparticles from platelets, thus transforming platelets to 'activated' phenotype. Both proteolysis of talin and microparticle release were precluded by calpeptin, a specific inhibitor of calpain. As microparticles are endowed with phosphatidylserine-enri...Continue Reading

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Citations

Nov 10, 2015·Transfusion and Apheresis Science : Official Journal of the World Apheresis Association : Official Journal of the European Society for Haemapheresis·Lacey JohnsonDenese C Marks
Feb 1, 2020·Journal of Extracellular Vesicles·Mariadelva Catalano, Lorraine O'Driscoll
Oct 6, 2020·Frontiers in Pharmacology·Enrica Urciuoli, Barbara Peruzzi
May 25, 2020·Biochemical and Biophysical Research Communications·Susheel N ChaurasiaDebabrata Dash

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