Document Detail


The antioxidant butylated hydroxytoluene (BHT) inhibits the dioctanoylglycerol-evoked platelet response but potentiates that elicited by ionomycin.
MedLine Citation:
PMID:  1314548     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Preincubation of aspirin-treated human platelets with butylated hydroxytoluene (BHT) inhibits secretion, aggregation, and protein phosphorylation induced by dioctanoylglycerol or phorbol 12-myristate 13-acetate (PMA). BHT alone elicits a rapid and transient phosphorylation of a 47-kDa protein, which is indistinguishable from the well-recognized major substrate of protein kinase C (PKC). Inhibition of diacylglycerol- or PMA-induced platelet activation is also observed after decay to the basal level of the BHT-evoked phosphorylation of the 47-kDa protein. By contrast BHT potentiates platelet responses elicited by the calcium ionophore ionomycin. In the presence of the PKC inhibitor staurosporine BHT fails to increase the ionomycin-promoted platelet aggregation, indicating that its effect occurs through a PKC activation, even if no correlation with the 47-kDa protein phosphorylation is observed. BHT does not significantly modify the affinity of protein kinase C purified from calf brain for Ca2+ or dioctanoylglycerol. It is concluded that: (a) a short exposure of platelets to BHT induces an activation, whereas a long exposure an inhibition of PKC, (b) at variance with diacylglycerols BHT decreases the platelet responses promoted by subsequent challenge with PKC activators themselves, and (c) similarly to other PKC activators BHT potentiates the cellular response elicited by calcium ionophores most likely by activating the phospholipase A2.
Authors:
M Ruzzene; M Francesconi; A Donella-Deana; A Alexandre; R Deana
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of biochemistry and biophysics     Volume:  294     ISSN:  0003-9861     ISO Abbreviation:  Arch. Biochem. Biophys.     Publication Date:  1992 May 
Date Detail:
Created Date:  1992-05-15     Completed Date:  1992-05-15     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372430     Medline TA:  Arch Biochem Biophys     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  724-30     Citation Subset:  IM    
Affiliation:
Department of Biological Chemistry, University of Padova, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / blood*
Alkaloids / pharmacology
Arachidonic Acid / pharmacology
Blood Platelets / drug effects,  physiology*
Butylated Hydroxytoluene / pharmacology*
Diglycerides / antagonists & inhibitors,  pharmacology*
Drug Synergism
Humans
Ionomycin / pharmacology*
Kinetics
Phorbol 12,13-Dibutyrate / metabolism
Phosphoprotein Phosphatases / blood*
Phosphoproteins / biosynthesis,  isolation & purification
Phosphorylation
Platelet Aggregation / drug effects*
Platelet Aggregation Inhibitors / pharmacology
Protein Kinase C / antagonists & inhibitors,  blood*,  isolation & purification
Staurosporine
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Diglycerides; 0/Phosphoproteins; 0/Platelet Aggregation Inhibitors; 1069-87-0/1,2-dioctanoylglycerol; 128-37-0/Butylated Hydroxytoluene; 37558-16-0/Phorbol 12,13-Dibutyrate; 506-32-1/Arachidonic Acid; 56-65-5/Adenosine Triphosphate; 56092-81-0/Ionomycin; 62996-74-1/Staurosporine; EC 2.7.11.13/Protein Kinase C; EC 3.1.3.16/Phosphoprotein Phosphatases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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