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Amino acid limitation regulates gene expression

Published online by Cambridge University Press:  28 February 2007

Alain Bruhat ,
Céline Jousse  and
Pierre Fafournoux
Alain Bruhat
Affiliation:
Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, 63122 Saint Genès Champanelle, France
Céline Jousse
Affiliation:
Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, 63122 Saint Genès Champanelle, France
Pierre Fafournoux*
Affiliation:
Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, 63122 Saint Genès Champanelle, France
*
*Corresponding Author: Dr Pierre Fafournoux, fax +33 473 62 45 70, email fpierre@clermont.inra.fr
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Abstract

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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.

Keywords

Gene expressionAmino acidsInsulin-like growth factor-binding protein-1
Type
Symposium on ‘Functionality of nutrients and gene expression’
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 3 , August 1999 , pp. 625 - 632
Copyright
Copyright © The Nutrition Society 1999

Footnotes

†

Contributed equally to the work presented in this paper.

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