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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
31
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pubmed:dateCreated |
1998-9-10
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pubmed:abstractText |
The thiol amino acid homocysteine (HC) accumulates in homocystinuria and homocyst(e)inemia, and is associated with a wide variety of clinical manifestations. To determine whether HC influences the cell's program of gene expression, vascular endothelial cells were treated with HC for 6-42 h and analyzed by differential display. We found a 3-7-fold, time-dependent induction of a 220-base pair fragment, which demonstrated complete sequence identity with elongation factor-1delta (EF-1delta), a member of the multimeric complex regulating mRNA translation. Fibroblasts from cystathionine beta-synthase -/- individuals also showed up to 3.0-fold increased levels of mRNA for EF-1alpha, -beta, and -delta when compared with normal cells, and treatment of normal cells with the HC precursor, methionine, induced a 1.5-2.0-fold increase in EF-1alpha, -beta, and -delta mRNA. This induction was completely inhibited by cycloheximide and reflected a doubling in the rate of gene transcription in nuclear run-on analyses. In HC-treated endothelial cells, pulse-chase studies revealed a doubling in the rate of synthesis of the thiol-containing protein, annexin II, but no change in synthesis of the cysteineless protein, plasminogen activator inhibitor-1. Thus, HC induces expression of a family of acute translational response genes through a protein synthesis-dependent transcriptional mechanism. This process may mediate accelerated synthesis of free thiol-containing proteins in response to HC-induced oxidative stress.
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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/Annexin A2,
http://linkedlifedata.com/resource/pubmed/chemical/Cycloheximide,
http://linkedlifedata.com/resource/pubmed/chemical/Cystathionine beta-Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Homocysteine,
http://linkedlifedata.com/resource/pubmed/chemical/Methionine,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Elongation Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Elongation Factors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
31
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pubmed:volume |
273
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
19840-6
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9677419-Amino Acid Sequence,
pubmed-meshheading:9677419-Annexin A2,
pubmed-meshheading:9677419-Base Sequence,
pubmed-meshheading:9677419-Cells, Cultured,
pubmed-meshheading:9677419-Cycloheximide,
pubmed-meshheading:9677419-Cystathionine beta-Synthase,
pubmed-meshheading:9677419-Endothelium, Vascular,
pubmed-meshheading:9677419-Gene Expression Regulation,
pubmed-meshheading:9677419-Homocysteine,
pubmed-meshheading:9677419-Humans,
pubmed-meshheading:9677419-Methionine,
pubmed-meshheading:9677419-Molecular Sequence Data,
pubmed-meshheading:9677419-Muscle, Smooth, Vascular,
pubmed-meshheading:9677419-Oxidative Stress,
pubmed-meshheading:9677419-Peptide Elongation Factor 1,
pubmed-meshheading:9677419-Peptide Elongation Factors,
pubmed-meshheading:9677419-Protein Biosynthesis,
pubmed-meshheading:9677419-RNA, Messenger,
pubmed-meshheading:9677419-Sulfhydryl Compounds,
pubmed-meshheading:9677419-Transcription, Genetic
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pubmed:year |
1998
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pubmed:articleTitle |
Induction of acute translational response genes by homocysteine. Elongation factors-1alpha, -beta, and -delta.
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pubmed:affiliation |
Divisions of Hematology-Oncology, Departments of Pediatrics and Medicine, Cornell University Medical College, New York, New York 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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