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rdf:type |
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lifeskim:mentions |
umls-concept:C0003695,
umls-concept:C0007634,
umls-concept:C0020053,
umls-concept:C0021641,
umls-concept:C0021670,
umls-concept:C0031667,
umls-concept:C0031676,
umls-concept:C0035820,
umls-concept:C0037083,
umls-concept:C0243126,
umls-concept:C0871261,
umls-concept:C1257890,
umls-concept:C1327616,
umls-concept:C1514559,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C1710082,
umls-concept:C2603343,
umls-concept:C2911692
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pubmed:issue |
16
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pubmed:dateCreated |
2001-4-17
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pubmed:abstractText |
A cytosolic 84-kDa group VIA phospholipase A(2) (iPLA(2)beta) that does not require Ca(2+) for catalysis has been cloned from several sources, including rat and human pancreatic islet beta-cells and murine P388D1 cells. Many potential iPLA(2)beta functions have been proposed, including a signaling role in beta-cell insulin secretion and a role in generating lysophosphatidylcholine acceptors for arachidonic acid incorporation into P388D1 cell phosphatidylcholine (PC). Proposals for iPLA(2)beta function rest in part on effects of inhibiting iPLA(2)beta activity with a bromoenol lactone (BEL) suicide substrate, but BEL also inhibits phosphatidate phosphohydrolase-1 and a group VIB phospholipase A(2). Manipulation of iPLA(2)beta expression by molecular biologic means is an alternative approach to study iPLA(2)beta functions, and we have used a retroviral construct containing iPLA(2)beta cDNA to prepare two INS-1 insulinoma cell clonal lines that stably overexpress iPLA(2)beta. Compared with parental INS-1 cells or cells transfected with empty vector, both iPLA(2)beta-overexpressing lines exhibit amplified insulin secretory responses to glucose and cAMP-elevating agents, and BEL substantially attenuates stimulated secretion. Electrospray ionization mass spectrometric analyses of arachidonic acid incorporation into INS-1 cell PC indicate that neither overexpression nor inhibition of iPLA(2)beta affects the rate or extent of this process in INS-1 cells. Immunocytofluorescence studies with antibodies directed against iPLA(2)beta indicate that cAMP-elevating agents increase perinuclear fluorescence in INS-1 cells, suggesting that iPLA(2)beta associates with nuclei. These studies are more consistent with a signaling than with a housekeeping role for iPLA(2)beta in insulin-secreting beta-cells.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1-Methyl-3-isobutylxanthine,
http://linkedlifedata.com/resource/pubmed/chemical/6-(bromomethylene)tetrahydro-3-(1-na...,
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Group VI Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/PLA2G6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylcholines,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipids,
http://linkedlifedata.com/resource/pubmed/chemical/Pla2g6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrones,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
20
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
13198-208
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:11278673-1-Methyl-3-isobutylxanthine,
pubmed-meshheading:11278673-Adenylate Cyclase,
pubmed-meshheading:11278673-Animals,
pubmed-meshheading:11278673-Arachidonic Acid,
pubmed-meshheading:11278673-Enzyme Inhibitors,
pubmed-meshheading:11278673-Forskolin,
pubmed-meshheading:11278673-Glucose,
pubmed-meshheading:11278673-Group VI Phospholipases A2,
pubmed-meshheading:11278673-Humans,
pubmed-meshheading:11278673-Insulin,
pubmed-meshheading:11278673-Insulinoma,
pubmed-meshheading:11278673-Kinetics,
pubmed-meshheading:11278673-Mice,
pubmed-meshheading:11278673-Naphthalenes,
pubmed-meshheading:11278673-Pancreatic Neoplasms,
pubmed-meshheading:11278673-Phosphatidylcholines,
pubmed-meshheading:11278673-Phospholipases A,
pubmed-meshheading:11278673-Phospholipases A2,
pubmed-meshheading:11278673-Phospholipids,
pubmed-meshheading:11278673-Pyrones,
pubmed-meshheading:11278673-Rats,
pubmed-meshheading:11278673-Recombinant Proteins,
pubmed-meshheading:11278673-Signal Transduction,
pubmed-meshheading:11278673-Spectrometry, Mass, Electrospray Ionization,
pubmed-meshheading:11278673-Substrate Specificity,
pubmed-meshheading:11278673-Transfection,
pubmed-meshheading:11278673-Tumor Cells, Cultured
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pubmed:year |
2001
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pubmed:articleTitle |
Studies of insulin secretory responses and of arachidonic acid incorporation into phospholipids of stably transfected insulinoma cells that overexpress group VIA phospholipase A2 (iPLA2beta ) indicate a signaling rather than a housekeeping role for iPLA2beta.
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pubmed:affiliation |
Mass Spectrometry Resource, Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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