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.
Jousse
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C
Unité de Nutrition Cellulaire et Moléculaire, INRA de Theix, 63122 Saint Genès Champanelle, France.
Bruhat
A
A
Ferrara
M
M
Fafournoux
P
P
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