Regulation of proteasome activity in activated human platelets

Abstract Ubiquitin-proteasome system has emerged a central player in regulation of diverse cellular processes. However, relevance of proteasome activity in platelets, which are terminally differentiated enucleate cells, is not clear. In this report we show that activation of platelets with physiolog...

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Bibliographic Details
Published in:Cell calcium (Edinburgh) 2011-04, Vol.49 (4), p.226-232
Main Authors: Nayak, Manasa K, Kumar, Kailash, Dash, Debabrata
Format: Article
Language:English
Subjects:
Advanced Basic Science
Blood Platelets - enzymology
Calcimycin - pharmacology
Calcium - metabolism
Calpain
Calpain - antagonists & inhibitors
Calpain - metabolism
Chelating Agents - pharmacology
Down-Regulation
Humans
Inositol 1,4,5-Trisphosphate Receptors - antagonists & inhibitors
Inositol 1,4,5-Trisphosphate Receptors - metabolism
Intracellular calcium
Platelet activation
Proteasome
Proteasome Endopeptidase Complex - chemistry
Proteasome Endopeptidase Complex - metabolism
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
Thapsigargin - pharmacology
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Summary:Abstract Ubiquitin-proteasome system has emerged a central player in regulation of diverse cellular processes. However, relevance of proteasome activity in platelets, which are terminally differentiated enucleate cells, is not clear. In this report we show that activation of platelets with physiological agonists was associated with 7–10 -fold rise in proteasomal activity. Elevation of cytosolic calcium with A23187 or thapsigargin resulted in significant increase in enzymatic activity, while treatment with intracellular calcium chelator or inhibitor of inositol trisphosphate receptor attenuated proteasomal enzymes in collagen-stimulated platelets. Specific inhibitors of protein kinase C as well as calpain, too, downregulated proteasome function. To conclude, proteasomal enzymatic activity in platelets is regulated by cytosolic calcium through Ca2+ -dependent downstream effectors like calpain and protein kinase C.
ISSN:0143-4160
1532-1991
DOI:10.1016/j.ceca.2011.02.005