Linked Life Data

2753227

Source:http://linkedlifedata.com/resource/pubmed/id/2753227

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
1989-8-31
pubmed:abstractText
We examined the mechanisms by which the phospholipid-sensitive, calcium-dependent protein kinase (protein kinase C) regulates prostacyclin synthesis by ovarian cells. In monolayer cultures of swine granulosa cells, specific phorbol esters significantly augmented production of the stable immunoreactive metabolite of prostacyclin, 6-keto-prostaglandin F1 alpha by 3- to 8-fold. These stimulatory actions were dose (0.03-30 ng/ml) and time (24-96 h) dependent, could be reproduced by non-diterpene activators of protein kinase C, and were corroborated by high performance liquid chromatography and mass spectrometry. The rank order of potency of phorbol esters was 12-O-tetradecanoylphorbol 13-acetate (TPA) greater than phorbol 12,13-dibenzoate greater than phorbol 12,13-dibutyrate greater than pure phorbol base. TPA enhanced de novo synthesis of prostacyclin, and synergized with the divalent cation ionophore, A23187. Although prostacyclin synthetase activity was not induced, microsomal cyclooxygenase activity was significantly increased by phorbol treatment. Moreover, TPA doubled the intracellular accumulation of free arachidonic acid. An inhibitor of phospholipase A2 (quinacrine 100 microM) impeded, whereas melittin (0.01 microM), an activator of cellular phospholipase A2, and purified bacterial phospholipase A2 (5 and 50 mU/ml) both augmented prostacyclin production. RH 59022 (30 microM), an inhibitor of diacylglyceride lipase, also suppressed prostacyclin synthesis. We conclude that the protein kinase C effector pathway is functionally coupled to de novo prostacyclin production in the swine granulosa cell. Increased eicosanoid synthesis can be accounted for by enhanced phospholipase A2 and diacylglyceride lipase-mediated availability of arachidonic acid substrate and an activated cyclooxygenase enzyme without a change in prostacyclin synthetase activity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0303-7207
pubmed:author
pubmed:issnType
Print
pubmed:volume
63
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
219-26
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Mechanism(s) by which activation of protein kinase C is coupled to prostacyclin synthesis in granulosa cells.
pubmed:affiliation
Department of Internal Medicine, University of Virginia School of Medicine, Charlottesville 22908.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.