Cholesterol can stimulate secretion of apolipoprotein B by cultured human hepatocytes

Kosykh, V. P.; Preobrazhensky, Sergey N.; Fuki, Ilia V.; Zaikina, O.E.; Tsibulsky, Vladimir P.; Repin, V. S.; Смирнов, В. Н.

doi:10.1016/0005-2760(85)90143-2

Cited by 41 publications

(8 citation statements)

References 12 publications

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“…In addition, a layer of polar, surface, lipids, including cholesterol and phospholipids, covers the surface area left unoccupied by apoB and provides the interaction required with the aqueous phase in the plasma [102]. The requirements for cholesterol [103,104] and for phosphatidylcholine synthesis [105] for the efficient production and secretion of VLDL by isolated perfused liver preparation or cultured hepatocytes have been described. Some general principles about apoB assembly with the hydrophobic core have been well established, but others remain to be determined.…”

Section: Assembly Of Vldl Particles In the Livermentioning

confidence: 99%

Role of insulin in hepatic fatty acid partitioning: emerging concepts

Zammit

1996

Biochemical Journal

114

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Section: Assembly Of Vldl Particles In the Livermentioning

confidence: 99%

Role of insulin in hepatic fatty acid partitioning: emerging concepts

Zammit

1996

Biochemical Journal

114

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“…For example, it is possible that the synthesis and secretion of cholesterol, which is stimulated by NEFA [8,9], may be rate-limiting for secretion of the VLDL. Interestingly, Kosykh et al [12] observed that secretion and synthesis of apolipoprotein (apo) B by human liver cells was stimulated by cholesterol, present in the incubation medium. In a comprehensive review, Vance & Vance [13] discussed the possible role which phospholipids, whose synthesis is increased by several NEFA [5], may play in the synthesis and secretion of lipoproteins by the liver.…”

Section: Introductionmentioning

confidence: 99%

Effects of oleic acid on the biosynthesis of lipoprotein apoproteins and distribution into the very-low-density lipoprotein by the isolated perfused rat liver

Salam

Wilcox

Heimberg

1988

Biochemical Journal

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The effects of oleic acid on the biosynthesis and secretion of VLDL (very-low-density-lipoprotein) apoproteins and lipids were investigated in isolated perfused rat liver. Protein synthesis was measured by the incorporation of L-[4,5-3H]leucine into the VLDL apoproteins (d less than 1.006) and into apolipoproteins of the whole perfusate (d less than 1.21). Oleate did not affect incorporation of [3H]leucine into total-perfusate or hepatic protein. The infusion of oleate, however, increased the mass and radioactivity of the VLDL apoprotein in proportion to the concentration of oleate infused. Uptake of oleate was similar with livers from fed or fasted animals. Fasting itself (24 h) decreased the net secretion and incorporation of [3H]leucine into total VLDL apoprotein and decreased the output of VLDL protein by the liver. A linear relationship existed between the output of VLDL triacylglycerol (mumol/h per g of liver) and secretion and/or synthesis of VLDL protein. Net output of VLDL cholesterol and phospholipid also increased linearly with VLDL-triacylglycerol output. Oleate stimulated incorporation of [3H]leucine into VLDL apo (apolipoprotein) E and apo C by livers from fed animals, and into VLDL apo Bh, B1, E and C by livers from fasted rats. The incorporation of [3H]leucine into individual apolipoproteins of the total perfusate lipoprotein (d less than 1.210 ultracentrifugal fraction) was not changed significantly by oleate during perfusion of livers from fed rats, suggesting that the synthesis de novo of each apolipoprotein was not stimulated by oleate. This is in contrast with that observed with livers from fasted rats, in which the synthesis of the total-perfusate lipoprotein (d less than 1.210 fraction) apo B, E and C was apparently stimulated by oleate. The observations with livers from fed rats suggest redistribution of radioactive apolipoproteins to the VLDL during or after the process of secretion, rather than an increase of apoprotein synthesis de novo. It appears, however, that the biosynthesis of apo B1, Bh, E and C was stimulated by oleic acid in livers from fasted rats. Since the incorporations of [3H]leucine into the VLDL and total-perfusate apolipoproteins were increased in fasted-rat liver when the fatty acid was infused, part of the apparent stimulated synthesis of the VLDL apoprotein may be in response to the increased formation and secretion of VLDL lipid.

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“…However, the oncogenic properties of Hep G2 cells restrict the extrapolation to non-cancerous human hepatocytes; the use of human hepatocytes is limited by difficulties in obtaining such cells and by the rapid degeneration of these cultured cells. Nevertheless, metabolic studies on cholesterol and lipoprotein carried out with healthy human hepatocytes have validated this human cell model (Kosykh et al, 1985;Sviridov et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture

Clerc

Sbarra

Domingo

et al. 1996

British J Pharmacology

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. The objective of this study was to compare in cultured human hepatocytes or Hep G2 cells, changes in the fate of unesterified low density lipoprotein (LDL)‐cholesterol induced by crilvastatin, a new cholesterol lowering drug and a reference statin, simvastatin. . The experiments were carried out for 20 h, each well contained 4.2 × 105/cm2 Hep G2 cells or 0.5 × 105/cm2 human hepatocytes, 130 μm ursodeoxycholate, 0.68 μCi or 1.59 μCi unesterified human [14C]‐LDL‐cholesterol, crilvastatin or simvastatin at 0 or 50 μm (both cell types) or 300 μm (Hep‐G2 cells). Incubation with the two drugs resulted in increased amounts of unesterified [14C]‐LDL‐cholesterol taken by the two cell types, compared to control. . Crilvastatin 50 μm led to significantly higher quantities of [14C]‐glyco‐ and [14C]‐tauro‐conjugated bile salts, compared to simvastatin. Statins reduced the apo B100 level secreted by the two cell types (simvastatin) or human hepatocytes (crilvastatin). Crilvastatin enhanced both the level of apo A1 secreted by the Hep G2 cells and the level of APF, a high density lipoprotein (HDL) and biliary apoprotein. . Crilvastatin not only acts by stimulating LDL‐cholesterol uptake by hepatocytes, but also by enhancing the catabolism of LDL‐cholesterol in bile salts and probably by stimulating HDL and/or bile component secretion. Such a mechanism was not previously described for HMG CoA reductase inhibitors. Our results on APF show that this apoprotein could be considered also as an indicator of changes in bile and/or HDL compartments. . The human hepatocyte model appeared to be a suitable and relevant model in the pharmacological***metabolic experiments carried out in this study. It led to more consistent data than those obtained with Hep G2 cells.

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Cholesterol can stimulate secretion of apolipoprotein B by cultured human hepatocytes

Cited by 41 publications

References 12 publications

Role of insulin in hepatic fatty acid partitioning: emerging concepts

Role of insulin in hepatic fatty acid partitioning: emerging concepts

Effects of oleic acid on the biosynthesis of lipoprotein apoproteins and distribution into the very-low-density lipoprotein by the isolated perfused rat liver

Differences in hypolipidaemic effects of two statins on Hep G2 cells or human hepatocytes in primary culture

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