Physiological concentration of amino acids regulates insulin-like-growth-factor-binding protein 1 expression

• Published in: Biochemical journal 1998-08, Vol.334 ( Pt 1) (1), p.147-153
• Main Authors: Jousse, C, Bruhat, A, Ferrara, M, Fafournoux, P
• Format: Article
• Language: English
• Subjects: Amino Acids - pharmacology; Amino Acids - physiology; Amino Acids, Essential - pharmacology; Animals; Biochemistry, Molecular Biology; Cells, Cultured; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Humans; Insulin-Like Growth Factor Binding Protein 1 - biosynthesis; Insulin-Like Growth Factor Binding Protein 1 - genetics; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor II - biosynthesis; Insulin-Like Growth Factor II - genetics; Kinetics; Life Sciences; Liver - drug effects; Liver - metabolism; Male; Rats; Rats, Inbred F344; RNA, Messenger - biosynthesis; Transcription, Genetic; Tumor Cells, Cultured
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3340147

Protein undernutrition is characterized by growth failure in young growing animals. Current evidence suggests that biosynthesis of insulin-like growth factor (IGF)-I and IGF-binding protein 1 (IGFBP-1) are key control points for nutritional regulation of growth. Here we examined the role of amino acid limitation in regulating the IGFBP-1 expression in the hepatic cell line. Our data show that leucine limitation strongly induces IGFBP-1 without affecting IGF-I and IGF-II expression in human HepG2 cells and in isolated rat hepatocytes. Depletion of arginine, cystine and all essential amino acids leads to induction of IGFBP-1 mRNA and protein expression in a dose-dependent manner. IGFBP-1 expression is significantly induced by leucine concentration in the range of that observed in the blood of rats fed a low-protein diet or in humans affected by kwashiorkor. Moreover, treatment of HepG2 cells with amino acids at a concentration reproducing the amino acid concentration found in portal blood of rats fed a low-protein diet leads to a significantly higher expression of IGFBP-1. These data represent the first demonstration that an amino acid limitation, as occurs during dietary protein deficiency, induces IGFBP-1 expression in hepatic cells. Therefore, amino acids by themselves can play, in concert with hormones, an important role in the control of gene expression.