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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
1998-6-30
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pubmed:abstractText |
Human mesangial cells (HMC) grown in high glucose environments synthesize excessive amounts of extracellular matrix proteins (ECM). The promoter regions of certain ECM genes contain TPA (phorbol ester)-responsive element (TRE) motifs that bind the transcription factor, activator protein-1 (AP-1), a complex of Jun and other phosphoproteins. AP-1 binding to the TRE promoter is regulated by the quantity, composition and post-translational modifications of proteins in the AP-1 complex. We report an increased binding of AP-1 to TRE oligonucleotides in HMC cultured chronically (5 days) in high glucose environments (30 mM d-glucose). This increased binding is not due to differences in the nuclear quantity of AP-1 proteins or in the composition of the AP-1 complex when compared to AP-1 proteins from cells grown in normal glucose (5 mM d-glucose). A 30 mM l-glucose environment also increased AP-1 binding, but to a degree less than d-glucose. The increased AP-1 binding was partly reversed by treatment of HMC with Calphostin C or Bisindolylmaleimide I suggesting a partial role of the protein kinase C (PKC) pathway in mediating AP-1 binding. AP-1 binding was unaffected by treatment of cells with the MEK inhibitor PD 98059. In addition, increased AP-1 binding persisted for at least 48 hours after media glucose concentrations were normalized. The level of Jun-NH2-terminal kinase (JNK) activity and the phosphorylation of the JNK kinase, SEK1, were unchanged by chronic high glucose concentrations. These studies suggest that in HMC cultured in chronic high glucose, post-translational modifications increase the binding of AP-1 to the TRE motif.
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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/Calcium-Calmodulin-Dependent...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Matrix Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide,
http://linkedlifedata.com/resource/pubmed/chemical/calphostin C
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0085-2538
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
53
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1172-81
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:9573531-Binding Sites,
pubmed-meshheading:9573531-Calcium-Calmodulin-Dependent Protein Kinases,
pubmed-meshheading:9573531-Cells, Cultured,
pubmed-meshheading:9573531-DNA,
pubmed-meshheading:9573531-Enzyme Inhibitors,
pubmed-meshheading:9573531-Extracellular Matrix Proteins,
pubmed-meshheading:9573531-Glomerular Mesangium,
pubmed-meshheading:9573531-Glucose,
pubmed-meshheading:9573531-Humans,
pubmed-meshheading:9573531-Indoles,
pubmed-meshheading:9573531-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:9573531-Kinetics,
pubmed-meshheading:9573531-MAP Kinase Kinase 4,
pubmed-meshheading:9573531-Maleimides,
pubmed-meshheading:9573531-Mitogen-Activated Protein Kinase Kinases,
pubmed-meshheading:9573531-Mitogen-Activated Protein Kinases,
pubmed-meshheading:9573531-Naphthalenes,
pubmed-meshheading:9573531-Promoter Regions, Genetic,
pubmed-meshheading:9573531-Protein Kinase C,
pubmed-meshheading:9573531-Protein Kinases,
pubmed-meshheading:9573531-Protein Processing, Post-Translational,
pubmed-meshheading:9573531-Transcription Factor AP-1
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pubmed:year |
1998
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pubmed:articleTitle |
DNA binding of activator protein-1 is increased in human mesangial cells cultured in high glucose concentrations.
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pubmed:affiliation |
Department of Medicine, Ohio State University, Columbus, USA. wilmer-1@medctr.osu.edu
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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