Linked Life Data

18496733

Source:http://linkedlifedata.com/resource/pubmed/id/18496733

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2008-6-25
pubmed:abstractText
We have earlier reported that the redox-active antioxidant, vitamin C (ascorbic acid), activates the lipid signaling enzyme, phospholipase D (PLD), at pharmacological doses (mM) in the bovine lung microvascular endothelial cells (BLMVECs). However, the activation of phospholipase A(2) (PLA(2)), another signaling phospholipase, and the modulation of PLD activation by PLA(2) in the ECs treated with vitamin C at pharmacological doses have not been reported to date. Therefore, this study aimed at the regulation of PLD activation by PLA(2) in the cultured BLMVECs exposed to vitamin C at pharmacological concentrations. The results revealed that vitamin C (3-10 mM) significantly activated PLA(2) starting at 30 min; however, the activation of PLD resulted only at 120 min of treatment of cells under identical conditions. Further studies were conducted utilizing specific pharmacological agents to understand the mechanism(s) of activation of PLA(2) and PLD in BLMVECs treated with vitamin C (5 mM) for 120 min. Antioxidants, calcium chelators, iron chelators, and PLA(2) inhibitors offered attenuation of the vitamin C-induced activation of both PLA(2) and PLD in the cells. Vitamin C was also observed to significantly induce the formation and release of the cyclooxygenase (COX)- and lipoxygenase (LOX)-catalyzed arachidonic acid (AA) metabolites and to activate the AA LOX in BLMVECs. The inhibitors of PLA(2), COX, and LOX were observed to effectively and significantly attenuate the vitamin C-induced PLD activation in BLMVECs. For the first time, the results of the present study revealed that the vitamin C-induced activation of PLD in vascular ECs was regulated by the upstream activation of PLA(2), COX, and LOX through the formation of AA metabolites involving oxidative stress, calcium, and iron.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0300-8177
pubmed:author
pubmed:issnType
Print
pubmed:volume
315
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-112
pubmed:meshHeading
pubmed-meshheading:18496733-Animals, pubmed-meshheading:18496733-Antioxidants, pubmed-meshheading:18496733-Arachidonic Acid, pubmed-meshheading:18496733-Ascorbic Acid, pubmed-meshheading:18496733-Calcium, pubmed-meshheading:18496733-Catalysis, pubmed-meshheading:18496733-Cattle, pubmed-meshheading:18496733-Dose-Response Relationship, Drug, pubmed-meshheading:18496733-Endothelial Cells, pubmed-meshheading:18496733-Enzyme Activation, pubmed-meshheading:18496733-Enzyme Inhibitors, pubmed-meshheading:18496733-Iron Chelating Agents, pubmed-meshheading:18496733-Lipid Metabolism, pubmed-meshheading:18496733-Lipoxygenase, pubmed-meshheading:18496733-Oxidation-Reduction, pubmed-meshheading:18496733-Phospholipase D, pubmed-meshheading:18496733-Phospholipases A2, pubmed-meshheading:18496733-Prostaglandin-Endoperoxide Synthases, pubmed-meshheading:18496733-Signal Transduction, pubmed-meshheading:18496733-Time Factors
pubmed:year
2008
pubmed:articleTitle
Redox-active antioxidant modulation of lipid signaling in vascular endothelial cells: vitamin C induces activation of phospholipase D through phospholipase A2, lipoxygenase, and cyclooxygenase.
pubmed:affiliation
Lipid Signaling and Lipidomics Laboratory, Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, College of Medicine, The Ohio State University, Columbus, OH, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural