Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
1998-9-10
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
31
pubmed:volume
273
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19840-6
pubmed:dateRevised
2007-11-14
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
pubmed:year
1998
pubmed:articleTitle
Induction of acute translational response genes by homocysteine. Elongation factors-1alpha, -beta, and -delta.
pubmed:affiliation
Divisions of Hematology-Oncology, Departments of Pediatrics and Medicine, Cornell University Medical College, New York, New York 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.