The effect of individual amino acids on apoB100 and Lp(a) secretion by HepG2 cells

• Published in: The Journal of biological chemistry Vol. 271; no. 46; pp. 29136 - 29145
• Main Authors: Cianflone, K. (McGill University, Montreal, Quebec, Canada.), Zhang, Z.J, Vu, H, Kohen-Avramoglu, R, Kalant, D, Sniderman, A.D
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 15.11.1996
• Subjects: ACIDE AMINE; Amino Acids - pharmacology; AMINOACIDOS; Animals; Apolipoprotein B-100; Apolipoproteins B - genetics; Apolipoproteins B - metabolism; ARN MENSAJERO; ARN MESSAGER; CELLULE; CELULAS; CHOLESTEROL; COLESTEROL; Cricetinae; ESTER; ESTERES; EXPRESION GENICA; EXPRESSION DES GENES; FOIE; HAMSTER; HIGADO; Humans; Lipid Metabolism; Lipoprotein(a) - metabolism; LIPOPROTEINAS; LIPOPROTEINE; PROTEINAS; PROTEINE; RNA, Messenger - genetics; SECRECION; SECRETION; TRIGLICERIDOS; TRIGLYCERIDE; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.271.46.29136

The rate at which HepG2 cells secrete apoB100 lipoproteins is inversely related to the concentration of amino acids in the medium (Zhang, Z., Sniderman, A. D., Kalant, D., Vu, H., Monge, J. C., Tao, Y., and Cianflone, K. (1993) J. Biol. Chem. 268, 26920-26926). The purpose of the present study was to determine the effect of individual amino acids on apoB100 and lipoprotein secretion. Asparagine was associated with modestly increased secretion. The branched chain amino acids (leucine isoleucine, and valine) and lysine had minor inhibitory effects. The other amino acids, by contrast, decreased apoB secretion, although the magnitude of the effect varied considerably, the most potent being tyrosine, cysteine, phenylalanine, tryptophan, methionine, and glutamine. Although the effect on Lp(a) generally paralleled that on apoB100, it was usually much less pronounced. No amino acid caused a marked decrease in albumin, apoAI, or total protein secreted from the HepG2 cells. The amino acid effect on apoB was paralleled by similar decreases in secreted cholesterol ester (CE) primarily in the low density lipoprotein density range (d 1.006-1.063 g/ml), although there was no significant change in intracellular CE. Neither intracellular nor secreted triglycerides (TG) or free cholesterol changed, resulting in a slightly larger TG-enriched particle being secreted. The effect was confirmed in cultured primary hamster hepatocytes, where a mixture of amino acids also caused a decrease in apoB secretion (up to 40%). ApoAI appeared to increase as with the HepG2 cells. Secreted CE paralleled apoB. There was no change in intracellular or secreted TG or free cholesterol, resulting in a substantially larger TG-rich particle being secreted. mRNA for apoB100 increased with asparagine, decreased moderately with branched chain amino acids, and decreased further with glutamine, as shown by dot blot and Northern blotting