Relationship between Amphipathic β Structures in the β1Domain of Apolipoprotein B and the Properties of the Secreted Lipoprotein Particles in McA-RH7777 Cells

Biochemistry ◽  
2017 ◽  
Vol 56 (31) ◽  
pp. 4084-4094
Author(s):  
Medha Manchekar ◽  
Richa Kapil ◽  
Zhihuan Sun ◽  
Jere P. Segrest ◽  
Nassrin Dashti
Keyword(s):  
Apolipoprotein B ◽  
Lipoprotein Particles

scholarly journals Palmitoylation of Apolipoprotein B Is Required for Proper Intracellular Sorting and Transport of Cholesteroyl Esters and Triglycerides

2000 ◽  
Vol 11 (2) ◽  
pp. 721-734 ◽  
Author(s):  
Yang Zhao ◽  
James B. McCabe ◽  
Jean Vance ◽  
Luc G. Berthiaume
Keyword(s):  
Apolipoprotein B ◽  
Neutral Lipids ◽  
Low Density Lipoproteins ◽  
Low Density ◽  
Hydrophobic Core ◽  
Wild Type ◽  
Very Low Density Lipoproteins ◽  
Structural Requirement ◽  
Lipoprotein Particles ◽  
Intracellular Sorting

Apolipoprotein B (apoB) is an essential component of chylomicrons, very low density lipoproteins, and low density lipoproteins. ApoB is a palmitoylated protein. To investigate the role of palmitoylation in lipoprotein function, a palmitoylation site was mapped to Cys-1085 and removed by mutagenesis. Secreted lipoprotein particles formed by nonpalmitoylated apoB were smaller and denser and failed to assemble a proper hydrophobic core. Indeed, the relative concentrations of nonpolar lipids were three to four times lower in lipoprotein particles containing mutant apoB compared with those containing wild-type apoB, whereas levels of polar lipids isolated from wild-type or mutant apoB lipoprotein particles appeared identical. Palmitoylation localized apoB to large vesicular structures corresponding to a subcompartment of the endoplasmic reticulum, where addition of neutral lipids was postulated to occur. In contrast, nonpalmitoylated apoB was concentrated in a dense perinuclear area corresponding to the Golgi compartment. The involvement of palmitoylation as a structural requirement for proper assembly of the hydrophobic core of the lipoprotein particle and its intracellular sorting represent novel roles for this posttranslational modification.

Abnormal concentrations of CII, CIII, and E apolipoproteins among apolipoprotein B-containing, B-free, and A-I-containing lipoprotein particles in hemodialysis patients

1991 ◽  
Vol 37 (3) ◽  
pp. 387-393 ◽  
Author(s):  
Naji Alsayed ◽  
RegIs Rebourcet
Keyword(s):  
Total Cholesterol ◽  
Apolipoprotein B ◽  
Marked Decrease ◽  
Hemodialysis Patients ◽  
Serum Concentrations ◽  
Dialysis Patients ◽  
Apo B ◽  
Lipoprotein Particles ◽  
Apo E ◽  
Anephric Patients

Abstract Serum concentrations of total cholesterol, triglycerides, and apolipoproteins (apo) A-I, B, CII, CIII, and E in 36 hemodialysis patients and nine anephric patients were compared with the concentrations in 34 normolipidemic subjects. The dialysis patients displayed a moderate hypertriglyceridemia (1.94 +/- 0.12 vs 1.09 +/- 0.11 mmol/L in controls, mean +/- SEM; P less than 0.001), apo CIII concentrations were also increased (130.2 +/- 2.1 vs 108.4 +/- 0.7 mg/L; P less than 0.001), whereas apo CII (34.5 +/- 0.5 vs 36 +/- 0.5 mg/L; P less than 0.05), apo E (22.7 +/- 0.3 vs 27.9 +/- 0.2 mg/L; P less than 0.001), and apo A-I (1.18 +/- 0.05 vs 1.31 +/- 0.04 g/L; P less than 0.05) were decreased. Concentrations of serum apo B were normal (0.86 +/- 0.03 vs 0.97 +/- 0.07 g/L). In the hemodialysis patients, apo CIII concentrations were increased in apo B-containing lipoproteins (30.1 +/- 0.5 vs 25.0 +/- 0.1 mg/L; P less than 0.001), whereas CII and E were decreased below control values (14.4 +/- 0.2 vs 16.8 +/- 0.1, and 8.2 +/- 0.2 vs 11.4 +/- 0.1 mg/L, respectively; P less than 0.001 each). By calculation, non-B-containing lipoproteins in the hemodialysis group had increased concentrations of apo CIII (100.1 +/- 2.1 vs 83.3 +/- 0.7 mg/L; P less than 0.001) and decreased amounts of apo E (14.5 +/- 0.4 vs 16.4 +/- 0.3 mg/L; P less than 0.001); apo CII content was unchanged (20.1 +/- 0.5 vs 19.3 +/- 0.5 mg/L). Results for apo CII, CIII, and E among apo A-I-containing lipoproteins in both normolipidemic and hemodialysis groups were similar to those in non-B-containing lipoproteins. Finally, the sole significant (P less than 0.01) difference between the anephric and hemodialysis groups was the lower apo E concentrations in the former group. Accumulation of triglyceride-rich lipoproteins in hemodialysis patients may thus be related to the enrichment of apo CIII in apo B-containing lipoproteins and to a marked decrease in the apo CII and E contents.

scholarly journals A role for palmitoylation in the quality control, assembly and secretion of apolipoprotein B

2004 ◽  
Vol 377 (1) ◽  
pp. 121-130 ◽  
Author(s):  
Gonzalo L. VILAS ◽  
Luc G. BERTHIAUME
Keyword(s):  
Quality Control ◽  
Apolipoprotein B ◽  
Neutral Lipids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Wild Type ◽  
Er Quality Control ◽  
Lipoprotein Particles ◽  
Secretion Efficiency

ApoB (apolipoprotein B)-containing lipoprotein particles, such as chylomicrons, very-low-density and low-density lipoprotein particles, transport triacylglycerol and cholesteryl esters in the bloodstream. A palmitoylation site was previously mapped to Cys-1085 in a functional truncated apoB variant (apoB-29) and abolished by mutagenesis. This Cys-1085Ser mutation resulted in secretion of smaller and denser lipoprotein particles containing 80% less cholesteryl ester and triacylglycerol than wild-type controls. We show that palmitoylation of apoB-29 occurs in the ER (endoplasmic reticulum), stimulates the ER–Golgi transport rate of apoB-29 almost 2-fold, doubles the secretion efficiency of wild-type apoB-29 in comparison with (Cys-1085Ser)apoB-29 and reduces significantly the association of wild-type apoB-29 with calnexin in comparison with (Cys-1085Ser)apoB-29. While non-palmitoylated apoB-29 co-localized extensively with constitutively secreted transferrin, wild-type apoB-29 did so only partially and was enriched in ER extensions. Our results suggest that palmitoylation of apoB regulates the biogenesis of nascent apoB-containing lipoprotein particles by concentrating apoB in a specialized ER compartment and by stimulating dissociation from constituents of the ER quality-control machinery. This reduced interaction would lead to a faster ER–Golgi transit time and a higher secretion efficiency of wild-type apoB-29. Palmitoylation could regulate the amount of apoB available for secretion of neutral lipids.

scholarly journals Assembly of Lipoprotein Particles Containing Apolipoprotein-B: Structural Model for the Nascent Lipoprotein Particle

2005 ◽  
Vol 88 (4) ◽  
pp. 2789-2800 ◽  
Author(s):  
Paul E. Richardson ◽  
Medha Manchekar ◽  
Nassrin Dashti ◽  
Martin K. Jones ◽  
Anne Beigneux ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Structural Model ◽  
Lipoprotein Particles ◽  
Lipoprotein Particle

Tunicamycin induces ubiquitination and degradation of apolipoprotein B in HepG2 cells

2001 ◽  
Vol 353 (3) ◽  
pp. 493-501 ◽  
Author(s):  
Wei LIAO ◽  
Lawrence CHAN
Keyword(s):  
Apolipoprotein B ◽  
Hepg2 Cells ◽  
Proteasome Inhibitor ◽  
Plasma Lipoproteins ◽  
Apo B ◽  
Net Production ◽  
Lipoprotein Particles ◽  
Essential Component ◽  
Intracellular Degradation

Apolipoprotein (apo) B-100 is an essential component of atherogenic plasma lipoproteins. Previous studies have demonstrated that the production of apoB-100 is regulated largely by intracellular degradation at both the co-translational and post-translational levels and that proteasome-mediated and non-proteasome-mediated pathways are involved in this process. ApoB-100 is a glycoprotein. The present study was undertaken to address the question of whether the inhibition of N-linked glycosylation with tunicamycin would interfere with apoB-100 production. We demonstrated that the treatment of HepG2 cells with tunicamycin decreased the net production of apoB-100 by enhancing co-translational degradation of the protein. This effect of tunicamycin was partly prevented by lactacystin, a specific proteasome inhibitor. Because lactacystin only partly reversed the effects of tunicamycin on apoB biogenesis, tunicamycin seemed also to induce apoB co-translational degradation in HepG2 cells by one or more non-proteasomal pathways. Furthermore, tunicamycin increased apoB ubiquitination approx. 4-fold. The proportion of the newly synthesized apoB-100 that was secreted and incorporated into the nascent lipoprotein particles was unaffected by tunicamycin. Thus the tunicamycin-mediated inhibition of N-linked glycosylation interferes with the production of apoB-100 that is mediated by both proteasomal and non-proteasomal pathways.

Clinical significance of apolipoprotein B containing lipoprotein particles

1990 ◽  
pp. 131-135
Author(s):  
J. C. Fruchart ◽  
J. M. Bard ◽  
H. J. Parra ◽  
I. Juhan-Vague ◽  
V. Clavey
Keyword(s):  
Clinical Significance ◽  
Apolipoprotein B ◽  
Lipoprotein Particles

scholarly journals Regulation of plasma LDL: the apoB paradigm

2009 ◽  
Vol 118 (5) ◽  
pp. 333-339 ◽  
Author(s):  
Allan D. Sniderman ◽  
Jacqueline De Graaf ◽  
Patrick Couture ◽  
Ken Williams ◽  
Robert S. Kiss ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Critical Aspect ◽  
Lipoprotein Particles ◽  
Ldl Particles ◽  
Plasma Compartment

The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholesterol homoeostasis in the hepatocyte. We believe that regulation of cholesterol homoeostasis within the hepatocyte is demonstrably more complex than envisioned by the LDL receptor paradigm, the conventional model to explain the regulation of plasma LDL and the fluxes of cholesterol into the liver, a model which was generated in the fibroblast but has never been fully validated in the hepatocyte. We suggest that the LDL receptor paradigm should be reconfigured as the apoB (apolipoprotein B) paradigm, which states that the rate at which LDL particles are produced is at least an important determinant of their concentration in plasma as the rate at which they are cleared from plasma and that secretion of cholesterol within VLDL (very-low-density lipoprotein) particles is an important mechanism of maintaining cholesterol homoeostasis within the hepatocyte. These two paradigms are not mutually exclusive. The LDL receptor paradigm, however, includes only one critical aspect of the regulation of plasma LDL, namely the rate at which LDL particles are cleared through the LDL receptor pathway, but ignores another – the rate at which LDL particles are added to the plasma compartment. The apoB paradigm includes both and points to a different model of how the hepatocyte achieves cholesterol homoeostasis in a complex metabolic environment.

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