Linked Life Data

8293040

Source:http://linkedlifedata.com/resource/pubmed/id/8293040

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1994-2-25
pubmed:abstractText
Use of the immunosuppressant drug cyclosporine A (CSA) has resulted in improved renal graft survival. However, an increased incidence of arterial and venous thrombotic diseases, hemolytic-uremic type syndrome, and findings resembling vasculitis in the kidneys of patients with CSA nephrotoxicity and accelerated atherogenesis have been reported. These disorders may be related to CSA-induced abnormalities in platelet function. We report here that CSA causes increased ADP-stimulated aggregation in isolated platelet suspensions indicating that CSA has a direct effect on platelet function, independent of CSA interactions with plasma factors. Maximal hyperaggregability of ADP-stimulated platelets occurred following a 1 h preincubation period with CSA. Hyperaggregability of platelets due to the presence of CSA was dose-dependent and approached plateau between 200-500 ng/ml CSA. We determined that CSA exerted its effects through a signal transduction pathway involving the phosphorylation of two intracellular proteins, a 40 kD substrate of PKC (p47) and the 20 kD light chain of myosin (p20), a substrate of calcium/calmodulin dependent kinase. Preincubation with CSA resulted in a 200% increase in the phosphorylation of these proteins in platelets stimulated with ADP. We conclude that CSA enhances ADP-induced platelet aggregation and secretion, in part, by potentiating the phosphorylative response of specific intracellular proteins to stimulation by agonists. This process may be responsible for the increased thrombosis and atherogenesis observed in CSA-treated patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0968-8773
pubmed:author
pubmed:issnType
Print
pubmed:volume
39
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
257-64
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Cyclosporine A enhances agonist-induced aggregation of human platelets by stimulating protein phosphorylation.
pubmed:affiliation
Department of Anatomy and Cell Biology, State University of New York Health Science Center at Brooklyn 11203.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't