Source:http://linkedlifedata.com/resource/pubmed/id/15096208
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2004-4-20
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pubmed:abstractText |
4-Hydroxy-2-trans-nonenal (4-HNE), one of the major end products of lipid peroxidation, has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. We show for the first time that incorporation of 4-HNE-metabolizing glutathione S-transferase (GST) isozyme, hGSTA4-4, into adherent cell lines HLE B-3 and CCL-75, by either cDNA transfection or microinjection of active enzyme, leads to their transformation. The dramatic phenotypic changes due to the incorporation of hGSTA4-4 include rounding of cells and anchorage-independent rapid proliferation of immortalized, rounded, and smaller cells. Incorporation of the inactive mutant of hGSTA4-4 (Y212F) in cells by either microinjection or transfection does not cause transformation, suggesting that the activity of hGSTA4-4 toward 4-HNE is required for transformation. This is further confirmed by the fact that mouse and Drosophila GST isozymes (mGSTA4-4 and DmGSTD1-1), which have high activity toward 4-HNE and subsequent depletion of 4-HNE, cause transformation whereas human GST isozymes hGSTP1-1 and hGSTA1-1, with minimal activity toward 4-HNE, do not cause transformation. In cells overexpressing active hGSTA4-4, expression of transforming growth factor beta1, cyclin-dependent kinase 2, protein kinase C betaII and extracellular signal regulated kinase is upregulated, whereas expression of p53 is downregulated. These studies suggest that alterations in 4-HNE homeostasis can profoundly affect cell-cycle signaling events.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4-hydroxy-2-nonenal,
http://linkedlifedata.com/resource/pubmed/chemical/Aldehydes,
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GSTA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/GstA protein, bacteria,
http://linkedlifedata.com/resource/pubmed/chemical/Isoenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0014-2956
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pubmed:author |
pubmed-author:AwasthiSanjayS,
pubmed-author:AwasthiYogesh CYC,
pubmed-author:BrownDavidD,
pubmed-author:PatrickBradB,
pubmed-author:SainiManjit KMK,
pubmed-author:SharmaAbhaA,
pubmed-author:SharmaRajendraR,
pubmed-author:SinghSharda PSP,
pubmed-author:SinghShivendra VSV,
pubmed-author:YangYusongY,
pubmed-author:ZimniakPiotrP
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pubmed:issnType |
Print
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pubmed:volume |
271
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1690-701
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15096208-Aldehydes,
pubmed-meshheading:15096208-Bacterial Proteins,
pubmed-meshheading:15096208-Carrier Proteins,
pubmed-meshheading:15096208-Cell Cycle,
pubmed-meshheading:15096208-Cell Division,
pubmed-meshheading:15096208-Cell Line, Transformed,
pubmed-meshheading:15096208-Cells, Cultured,
pubmed-meshheading:15096208-Glutathione,
pubmed-meshheading:15096208-Glutathione Transferase,
pubmed-meshheading:15096208-Humans,
pubmed-meshheading:15096208-Isoenzymes,
pubmed-meshheading:15096208-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:15096208-Microinjections,
pubmed-meshheading:15096208-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15096208-Transfection
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pubmed:year |
2004
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pubmed:articleTitle |
Transfection with 4-hydroxynonenal-metabolizing glutathione S-transferase isozymes leads to phenotypic transformation and immortalization of adherent cells.
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pubmed:affiliation |
Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, TX 77555-0647, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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