Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-10T14:12:10.386Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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.

References

Baertl, JM, Placko, RP & Graham, GG (1974) Serum proteins and plasma free amino acids in severe malnutrition. American Journal of Clinical Nutrition 27, 733–742.CrossRefGoogle ScholarPubMed
Baker, J, Liu, JP, Robertson, EJ & Efstratiadis, A (1993) Role of insulin-like growth factors in embryonic and postnatal growth. Cell 75, 73–82.CrossRefGoogle ScholarPubMed
Barlett, JD, Luethy, JD, Carlson, SG, Sollott, SJ & Holbrook, NJ (1992) Calcium ionophore A23187 induces expression of the growth arrest and DNA damage inducible CCAAT/enhancer-binding protein (C/EBP)-related gene gadd153, Journal of Biological Chemistry 267, 20465–20470.CrossRefGoogle Scholar
Binoux, M (1995) The IGF system in metabolism regulation. Diabetes and Metabolism 21, 330–337.Google ScholarPubMed
Brismar, K, Gutniak, M, Povoa, G, Werner, S & Hall, K (1988) Insulin regulates the 35 kDa IGF binding protein in patients with diabetes mellitus. Journal of Endocrinological Investigation 11, 599–602.CrossRefGoogle ScholarPubMed
Bruhat, A, Jousse, C, Wang, XZ, Ron, D, Ferrara, M & Fafournoux, P (1997) Amino acid limitation induces expression of CHOP, a CCAAT/enhancer binding protein-related gene, at both transcriptional and post-transcriptional levels. Journal of Biological Chemistry 272, 17588–17593.CrossRefGoogle Scholar
Busby, WH, Snyder, DK & Clemmons, DR (1988) Radio-immunoassay of 26, 000-dalton plasma insulin-like growth factor-binding protein: control by nutritional variables. Journal of Clinical Endocrinology and Metabolism 67, 11225–11230.CrossRefGoogle Scholar
Carlson, SG, Fawcett, TW, Barlett, JD, Bernier, M & Holbrook, NJ (1993) Regulation of the C/EBP-related gene gadd153 by glucose deprivation. Molecular and Cellular Biology 13, 4736–4744.Google Scholar
Cotterill, AM, Cowell, CT, Baxter, RC, McNeil, D & Silinik, M (1988) Regulation of the growth hormone-independent growth factor-binding protein in children. Journal of Clinical Endocrinology and Metabolism 67, 882–887.CrossRefGoogle ScholarPubMed
Coward, WA & Lunn, PG (1981) The biochemistry and physiology of kwashiorkor and marasmus. British Medical Bulletin 37, 19–24.CrossRefGoogle ScholarPubMed
Donovan, SM, Atilano, LC, Hintz, RL, Wilson, DM & Rosenfeld, RG (1991) Differential regulation of the insulin-like growth factors (IGF-I and -II) and IGF binding proteins during malnutrition in the neonatal rat. Endocrinology 129, 149–157.CrossRefGoogle ScholarPubMed
Fafournoux, P, Rémésy, C & Demigné, C (1990) Fluxes and membrane transport of amino acids in rat liver under different protein diets. American Journal of Physiology 259, E614–E625.Google ScholarPubMed
Fornace, AJ, Alamo, J Jr & Hollander, MC (1988) DNA damage-inducible transcripts in mammalian cells. Proceedings of the National Academy of Sciences USA 85, 8800–8804.CrossRefGoogle ScholarPubMed
Gay, E, Seurin, D, Babajko, S, Doublier, S, Cazillis, M & Binoux, M (1997) Liver-specific expression of human insulin-like growth factor binding protein-1 in transgenic mice: Repercussions on reproduction, ante- and perinatal mortality and postnatal growth. Endocrinology 138, 2937–2947.CrossRefGoogle ScholarPubMed
Girard, J, Perdereau, D, Foufelle, F, Prip-Buus, C & Ferré, P (1994) Regulation of lipogenic enzyme gene expression by nutrients and hormones. FASEB Journal 8, 36–42.CrossRefGoogle ScholarPubMed
Grimble, RF & Whitehead, RG (1970) Fasting serum-amino acid patterns in kwashiorkor and after administration of different levels of protein. Lancet i, 918–920.CrossRefGoogle Scholar
Gurney, AL, Pak, EA, Liu, J, Giralt, M, McGrane, MM, Patel, YM, Crawford, DR, Nizielski, SE, Savon, S & Hanson, RW (1994) Metabolic regulation of gene transcription. Journal of Nutrition 124, 1533S–1539S.CrossRefGoogle ScholarPubMed
Jackson, AA & Grimble, RF (1990) Malnutrition and amino acid metabolism. In The Malnourished Child. Nestle Nutrition Workshop Series, vol. 19, pp. 73–94 [Suskind, RM and Suskind, LL, editors]. New York: Vevey Raven Press.Google Scholar
Jousse, C, Bruhat, A, Ferrara, M & Fafournoux, P (1998) Physiological concentration of amino acids regulates insulin-like-growth-factor-binding protein 1 expression. Biochemical Journal 334, 147–153.CrossRefGoogle ScholarPubMed
Kilberg, MS, Hutson, RG & Laine, RO (1994) Amino acid-regulated gene expression in eukaryotic cells. FASEB Journal 8, 13–19.CrossRefGoogle ScholarPubMed
Kita, K, Tomas, FM, Owens, PC, Knowles, SE, Forbes, BE, Upton, Z, Hughes, R & Ballard, FJ (1996) Influence of nutrition on hepatic IGF-I mRNA levels and plasma concentrations of IGF-I and IGF-II in meat-type chickens. Journal of Endocrinology 149, 181–190.CrossRefGoogle ScholarPubMed
Lee, PDK, Conover, CA & Powell, DR (1993) Regulation and function of insulin-like growth factor-binding protein-1. Proceedings of the Society for Experimental Biology and Medicine 204, 4–29.CrossRefGoogle ScholarPubMed
Lewitt, MS, Denyer, GS, Cooney, GJ & Baxter, RC (1991) Insulin-like growth factor-binding protein-1 modulates blood glucose levels. Endocrinology 129, 2254–2256.CrossRefGoogle ScholarPubMed
Luethy, JD & Holbrook, NJ (1992) The pathway regulating GADD153 induction in response to DNA damage is independent of protein kinase C and tyrosine kinases. Cancer Research 54, 1902S–1906S.Google Scholar
Palacin, M, Estévez, R, Bertran, J & Zorzano, A (1998) Molecular biology of mammalian plasma membrane amino acid transporters. Physiological Review 78, 969–1045.CrossRefGoogle ScholarPubMed
Rajkumar, K, Barron, D, Lewitt, MS & Murphy, LJ (1995) Growth retardation and hyperglycemia in insulin-like growth factor binding protein-1 transgenic mice. Endocrinology 136, 4029–4034.CrossRefGoogle ScholarPubMed
Rajkumar, K, Krsek, M, Dheen, ST & Murphy, LJ (1996) Impaired glucose homeostasis in insulin-like growth factor binding protein-1 transgenic mice. Journal of Clinical Investigation 98, 1818–1825.CrossRefGoogle ScholarPubMed
Straus, DS (1994) Nutritional regulation of hormones and growth factors that control mammalian growth. FASEB Journal 8, 6–12.CrossRefGoogle ScholarPubMed
Straus, DS, Burke, EJ & Marten, NW (1993) Induction of insulin-like growth factor binding protein-1 gene expression in liver of protein-restricted rats and in rat hepatoma cells limited for a single amino acid. Endocrinology 132, 1090–1100.CrossRefGoogle ScholarPubMed
Straus, DS & Takemoto, CD (1990) Effect of dietary protein deprivation on insulin-like growth factor-I and -II, IGF binding protein-2, and serum albumin gene expression in rat. Endocrinology 127, 1849–1860.CrossRefGoogle ScholarPubMed
Suikkari, AM, Koivisto, VA, Rutanen, EM, Yki-Järvinen, H, Karonen, SL & Seppälä, M (1988) Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. Journal of Clinical Endocrinology and Metabolism 66, 266–272.CrossRefGoogle ScholarPubMed
Sylvester, SL, ap Rhys, CMJ, Luethy-Martindale, JD & Holbrook, NJ (1994) Induction of GADD153, a CCAAT-enhancer-binding protein (C/EBP)-related gene, during the acute phase response in rats. Journal of Biological Chemistry 269, 20119–20125.CrossRefGoogle ScholarPubMed
Towle, HC (1995) Metabolic regulation of gene transcription in mammals. Journal of Biological Chemistry 270, 23235–23238.CrossRefGoogle ScholarPubMed
Vance, ML, Hartman, ML & Thorner, MO (1992) Growth hormone and nutrition. Hormone Research 38, 85–88.CrossRefGoogle ScholarPubMed
Vaulont, S & Kahn, A (1994) Transcriptional control of metabolic regulation genes by carbohydrates. FASEB Journal 8, 28–35.CrossRefGoogle ScholarPubMed
Walton, PE, Dunshea, FR & Ballard, FJ (1995) In vivo actions of IGF analogues with poor affinities for IGFBPs: metabolic and growth effects in pigs of different ages and GH responsiveness. Proceedings of Growth Factor Research 6, 385–395.CrossRefGoogle ScholarPubMed
Wang, X-Z, Lawson, B, Brewer, JW, Zinszner, H, Sanjay, A, Mi, L-J, Boorstein, R, Kreibich, G, Hendershot, LM & Ron, D (1996) Signals from the stressed endoplasmic reticulum induce C/EBP-homologous protein (CHOP). Molecular and Cellular Biology 16, 4273–4280.CrossRefGoogle ScholarPubMed
Wang, ZZ, Kuroda, M, Sok, J, Batchvarova, N, Kimmel, R, Chung, P, Zinszner, H & Ron, D (1988) Identification of novel stress-induced genes downstream of chop. EMBO Journal 17, 3619–3630.CrossRefGoogle Scholar