Mallick 2015 Cell Calcium

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Mallick RL, Kumari S, Singh N, Sonkar VK, Dash D (2015) Prion protein fragment (106-126) induces prothrombotic state by raising platelet intracellular calcium and microparticle release. Cell Calcium 57:300-11.

» PMID: 25749016

Mallick RL, Kumari S, Singh N, Sonkar VK, Dash D (2015) Cell Calcium

Abstract: Prion diseases are neurodegenerative disorders where infectious prion proteins (PrP) accumulate in brainleading to aggregation of amyloid fibrils and neuronal cell death. The amino acid sequence 106–126 fromprion proteins, PrP(106–126), is highly amyloidogenic and implicated in prion-induced pathologies. AsPrP 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) (20 µM) induced dramatic 30-fold rise in intracellular calcium (from 105 ± 30 to 3425 ± 525 nM) 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-enriched surface and hence are pro-coagulant in nature, exposure to prion favored a thrombogenic state in the organism.

Keywords: Prion, Platelets, Intracellular calcium, Calpain, Microparticles

O2k-Network Lab: US NC Durham Li PA, IN Varanasi Dash D, IN Haldia Chakrabarti S


Labels: MiParea: Respiration  Pathology: Neurodegenerative 

Organism: Human  Tissue;cell: Blood cells, Platelet  Preparation: Intact cells 


Coupling state: ROUTINE  Pathway: ROX  HRR: Oxygraph-2k