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Related Experiment Videos

Amino acid limitation regulates gene expression.

A Bruhat1, C Jousse, P Fafournoux

  • 1Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, Saint Genès Champanelle, France.

The Proceedings of the Nutrition Society
|December 22, 1999
PubMed
Summary

Amino acid limitation, such as from low protein diets, significantly impacts mammalian gene expression. This study reveals how deficiencies in specific amino acids, like leucine, trigger the expression of key proteins such as insulin-like growth factor-binding protein-1 (IGFBP-1) and CCAAT/enhancer-binding protein homologous protein (CHOP).

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Area of Science:

  • Molecular Biology
  • Nutritional Biochemistry
  • Mammalian Physiology

Background:

  • Plasma amino acid concentrations are sensitive to nutritional and pathological states in mammals.
  • Deficiencies or imbalances in dietary amino acids can alter the overall amino acid profile.

Purpose of the Study:

  • To investigate the role of amino acid limitation in regulating mammalian gene expression.
  • To elucidate the molecular mechanisms underlying amino acid-mediated gene regulation.

Main Methods:

  • Depletion of specific amino acids (arginine, cystine, essential amino acids, leucine) in cell cultures and animal models.
  • Quantification of mRNA and protein expression for IGFBP-1 and CHOP.
  • Analysis of gene transcription rates and mRNA stability.

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  • Identification of regulatory elements within the CHOP gene.

    • Main Results:

    • Depletion of arginine, cystine, and essential amino acids induced insulin-like growth factor-binding protein-1 (IGFBP-1) mRNA and protein expression.
    • Exposure to low amino acid concentrations, mimicking portal blood from low-protein diets, significantly increased IGFBP-1 expression in HepG2 cells.
    • Leucine deprivation led to the induction of CCAAT/enhancer-binding protein homologous protein (CHOP) mRNA and protein.
    • Elevated CHOP mRNA resulted from increased transcription rates and enhanced mRNA stability.
    • Specific elements in the CHOP gene were identified as crucial for transcriptional activation under amino acid limitation.

    Conclusions:

    • Dietary protein deficiency and resulting amino acid limitation can directly induce gene expression in mammals.
    • Amino acids play a significant role in controlling gene expression, acting in conjunction with hormonal signals.
    • The study identified molecular pathways through which amino acid availability regulates the expression of specific genes like IGFBP-1 and CHOP.