Abstract
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. Pulse-chase studies indicated that there was no change in apoB secretion efficiency under any condition. These results extend our previous observations by demonstrating specificity of the amino acid effect on apoB100 secretion. Although an effect on transcription is the likely mechanism, the exact basis for this remains to be determined.
Highlights
These results extend our previous observations by demonstrating specificity of the amino acid effect on apoB100 secretion
Amino acids alter the rate of apoB100 synthesis but do not alter the secretion efficiency from HepG2 cells [10]; i.e. as amino acid concentration in the medium is increased, apoB100 synthetic rates decrease without any change in the proportion of molecules that are degraded intracellularly
We have previously reported in abstract form that Lp(a) particles are secreted by HepG2 cells and that there is an inverse relation between their secretion and ambient amino acid concentration as there is with apoB100 lipoproteins [11]
Summary
These results extend our previous observations by demonstrating specificity of the amino acid effect on apoB100 secretion. Albumin affects secretion of apoB100 particles, with lower concentrations in the medium being associated with higher rates of apoB100 secretion This effect may relate to concurrent changes in intracellular CE synthesis [8, 9]. Amino acids alter the rate of apoB100 synthesis but do not alter the secretion efficiency from HepG2 cells [10]; i.e. as amino acid concentration in the medium is increased, apoB100 synthetic rates decrease without any change in the proportion of molecules that are degraded intracellularly. There is considerable similarity, the effects of individual amino acids on apoB100 and Lp(a) secretion are not identical This effect was not confined to HepG2 cells. Studies in cultured primary hamster hepatocytes confirmed that amino acids decrease apoB secretion in this model as well
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