Physiological concentration of amino acids regulates insulin-like-growth-factor-binding protein 1 expression.
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.
Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, 63122 Saint Genès Champanelle, France.
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Jousse
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Bruhat
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Ferrara
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Fafournoux
D000596:Amino Acids / Q000494:pharmacology / Q000502:physiology*; D000601:Amino Acids, Essential / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000096:biosynthesis / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis / Q000235:genetics; D007335:Insulin-Like Growth Factor II / Q000096:biosynthesis / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D000596:Amino Acids; D000601:Amino Acids, Essential; D018970:Insulin-Like Growth Factor Binding Protein 1; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II