title: Intracellular apoprotein B degradation is suppressed by decreased albumin concentration in Hep G2 cells.
abstract: It is generally accepted that hepatic secretion of apoprotein (apo) B-containing lipoproteins is substantially increased in nephrosis. To elucidate the mechanisms for the oversecretion of apo B, we investigated the effect of a various concentration of albumin on apo B kinetics in the absence or presence of oleate in Hep G2 cells. Hep G2 cells were labeled with [3H]-leucine in leucine-free medium containing 0, 1.5, 3.0 or 4.5% BSA for 180 minutes, and the secreted radiolabeled apo B, apo A1 and albumin were isolated by immunoprecipitation and counted. The secretions of apo B and albumin were suppressed by BSA (bovine serum albumin) in a dose-dependent manner, but the secretion of apo A1 was not suppressed significantly. Oleate (0.4 mM) increased the rate of apo B secretion by 2.5-fold when oleate was bound to 1.5% BSA, but at higher concentrations of BSA (3.0 or 4.5%), apo B secretion was less responsive to oleate. A pulse-chase study indicated that early apo B degradation was significantly suppressed in cells incubated with lower concentrations of BSA (0 or 1.5% BSA), thereby rapidly stimulating apo B secretion. Oleate (0.4 mM) potently inhibited apo B degradation when oleate was bound to 1.5% BSA, whereas the inhibition was not observed when oleate was bound to 4.5% BSA. Intracellular albumin synthesis was stimulated in BSA-free medium, but intracellular decay of albumin was essentially unaffected by concentration of BSA. Similar to BSA, a higher concentration of dextran (3.0 or 4.5%) reduced apo B secretion, and this was the result of increased early apo B degradation in the cells. These results indicate that reduced albumin suppresses intracellular apo B degradation, and the inhibition of apo B degradation by oleate is manifested only at a low concentration of albumin. Therefore, the present study suggests that free fatty acids bound to low concentration of albumin in the circulating plasma play an important role on hepatic oversecretion of apo B-containing lipoprotein in hypoalbuminemic state, such as nephrotic syndrome.
authors.affiliation: First Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Hirano
authors.forename: S
authors.initials: S
authors.lastname: Furukawa
authors.forename: M
authors.initials: M
authors.lastname: Kurokawa
authors.forename: T
authors.initials: T
authors.lastname: Ebara
authors.forename: J L
authors.initials: JL
authors.lastname: Dixon
authors.forename: S
authors.initials: S
authors.lastname: Nagano
mesh_terms: D016632:Apolipoprotein A-I / Q000378:metabolism; D001055:Apolipoproteins B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D003470:Culture Media / Q000378:metabolism; D003911:Dextrans / Q000494:pharmacology; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D007700:Kinetics; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D019301:Oleic Acid; D009829:Oleic Acids / Q000494:pharmacology; D009994:Osmolar Concentration; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D016632:Apolipoprotein A-I; D001055:Apolipoproteins B; D003470:Culture Media; D003911:Dextrans; D009829:Oleic Acids; D012709:Serum Albumin; D012710:Serum Albumin, Bovine; D019301:Oleic Acid