Document Detail

Amino acid limitation regulates gene expression.
MedLine Citation:
PMID:  10604196     Owner:  NLM     Status:  MEDLINE    
In mammals, the plasma concentration of amino acids is affected by nutritional or pathological conditions. For example, an alteration in the amino acid profile has been reported when there is a deficiency of any one or more of the essential amino acids, a dietary imbalance of amino acids, or an insufficient intake of protein. We examined the role of amino acid limitation in regulating mammalian gene expression. Depletion of arginine, cystine and all essential amino acids leads to induction of insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression in a dose-dependent manner. Moreover, exposure of HepG2 cells to amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed on a low-protein diet leads to a significantly higher (P < 0.0002) expression of IGFBP-1. Using CCAAT/enhancer-binding protein homologous protein (CHOP) induction by leucine deprivation as a model, we have characterized the molecular mechanisms involved in the regulation of gene expression by amino acids. We have shown that leucine limitation leads to induction of CHOP mRNA and protein. Elevated mRNA levels result from both an increase in the rate of CHOP transcription and an increase in mRNA stability. We have characterized two elements of the CHOP gene that are essential to the transcriptional activation produced by an amino acid limitation. These findings demonstrate that an amino acid limitation, as occurs during dietary protein deficiency, can induce gene expression. Thus, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.
A Bruhat; C Jousse; P Fafournoux
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  The Proceedings of the Nutrition Society     Volume:  58     ISSN:  0029-6651     ISO Abbreviation:  Proc Nutr Soc     Publication Date:  1999 Aug 
Date Detail:
Created Date:  2000-01-20     Completed Date:  2000-01-20     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7505881     Medline TA:  Proc Nutr Soc     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  625-32     Citation Subset:  IM    
Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, Saint Genès Champanelle, France.
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MeSH Terms
Amino Acids / administration & dosage,  deficiency,  physiology*
CCAAT-Enhancer-Binding Proteins*
DNA-Binding Proteins / genetics
Dietary Proteins / administration & dosage
Gene Expression Regulation*
Insulin-Like Growth Factor Binding Protein 1 / genetics
Transcription Factor CHOP
Transcription Factors / genetics
Reg. No./Substance:
0/Amino Acids; 0/CCAAT-Enhancer-Binding Proteins; 0/DDIT3 protein, human; 0/DNA-Binding Proteins; 0/Dietary Proteins; 0/Insulin-Like Growth Factor Binding Protein 1; 0/Transcription Factors; 147336-12-7/Transcription Factor CHOP

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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