Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis

Olofsson, Sven-Olof; Borén, Jan

doi:10.1111/j.1365-2796.2005.01556.x

Cited by 258 publications

(207 citation statements)

References 126 publications

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“…full lipidation of apoB-lipoproteins to VLDL buoyancy occurs post-ER (35)(36)(37). Also, given the conspicuous physical barriers against translocating large, extensively lipidated apoBlipoproteins out of the secretory pathway, which would be required for the proteasome to have access to them, the autophagosomal/lysosomal system may be the only plausible mechanism for late-stage quality control of these particles.…”

Section: Discussionmentioning

confidence: 99%

Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control

Pan

Maitin

Parathath

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

117

108

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Hepatic secretion of apolipoprotein-B (apoB), the major protein of atherogenic lipoproteins, is regulated through posttranslational degradation. We reported a degradation pathway, post-ER presecretory proteolysis (PERPP), that is increased by reactive oxygen species (ROS) generated within hepatocytes from dietary polyunsaturated fatty acids (PUFA). We now report the molecular processes by which PUFA-derived ROS regulate PERPP of apoB. ApoB exits the ER; undergoes limited oxidant-dependent aggregation; and then, upon exit from the Golgi, becomes extensively oxidized and converted into large aggregates. The aggregates slowly degrade by an autophagic process. None of the oxidized, aggregated material leaves cells, thereby preventing export of apoBlipoproteins containing potentially toxic lipid peroxides. In summary, apoB secretory control via PERPP/autophagosomes is likely a key component of normal and pathologic regulation of plasma apoB levels, as well as a means for remarkably late-stage quality control of a secreted protein.

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Section: Discussionmentioning

confidence: 99%

Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control

Pan

Maitin

Parathath

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

117

108

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“…Owing to its role in lipid transport and cholesterol homeostasis, it is not surprising that increased levels of ApoB100 plays a central role in the increased risk of vascular disease and the development of atherosclerosis. 61 Additionally, it has been reported that visceral obesity can lead to overproduction of ApoB100. 62 The current data indicate a reduction in most peptide components for apo B-100, which differentiated the autism group as a whole from typical children as well as differentiating between LFA and HFA children.…”

Section: Apolipoproteinsmentioning

confidence: 99%

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Corbett

Kantor²,

Schulman³

et al. 2006

Mol Psychiatry

161

113

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Modern methods that use systematic, quantitative and unbiased approaches are making it possible to discover proteins altered by a disease. To identify proteins that might be differentially expressed in autism, serum proteins from blood were subjected to trypsin digestion followed by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) on time-of-flight (TOF) instruments to identify differentially expressed peptides. Children with autism 4-6 years of age (n = 69) were compared to typically developing children (n = 35) with similar age and gender distributions. A total of 6348 peptide components were quantified. Of these, five peptide components corresponding to four known proteins had an effect size > 0.99 with a P < 0.05 and a Mascot identification score of 30 or greater for autism compared to controls. The four proteins were: Apolipoprotein (apo) B-100, Complement Factor H Related Protein (FHR1), Complement C1q and Fibronectin 1 (FN1). In addition, apo B-100 and apo A-IV were higher in children with high compared to low functioning autism. Apos are involved in the transport of lipids, cholesterol and vitamin E. The complement system is involved in the lysis and removal of infectious organisms in blood, and may be involved in cellular apoptosis in brain. Despite limitations of the study, including the low fold changes and variable detection rates for the peptide components, the data support possible differences of circulating proteins in autism, and should help stimulate the continued search for causes and treatments of autism by examining peripheral blood.

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“…Assembly of VLDL starts with the cotranslational lipidation of apoB-100 by microsomal triglyceride transfer protein delivering lipids from cytosolic lipid droplets into the endoplasmic reticulum lumen (32,33). The resulting primordial lipoprotein is further lipidated into a triglyceride-poor form of VLDL that is released from the endoplasmic reticulum at distinct exit sites and transported to the Golgi apparatus.…”

Section: Flagmentioning

confidence: 99%

Biochemical and Morphological Properties of Hepatitis C Virus Particles and Determination of Their Lipidome

Merz

Long

Hiet

et al. 2011

Journal of Biological Chemistry

312

355

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A hallmark of hepatitis C virus (HCV) particles is their association with host cell lipids, most notably lipoprotein components. It is thought that this property accounts for the low density of virus particles and their large heterogeneity. However, the composition of infectious virions and their biochemical and morphological properties are largely unknown. We developed a system in which the envelope glycoprotein E2 was Nterminally tagged with a FLAG epitope. This virus, designated Jc1E2 FLAG , produced infectivity titers to wild type levels and allowed affinity purification of virus particles that were analyzed for their protein and lipid composition. By using mass spectrometry, we found the lipid composition of Jc1E2 FLAG particles to resemble the one very low-and low density-lipoprotein with cholesteryl esters accounting for almost half of the total HCV lipids. Thus, HCV particles possess a unique lipid composition that is very distinct from all other viruses analyzed so far and from the human liver cells in which HCV was produced. By electron microscopy (EM), we found purified Jc1E2 FLAG particles to be heterogeneous, mostly spherical structures, with an average diameter of about 73 nm. Importantly, the majority of E2-containing particles also contained apoE on their surface as assessed by immuno-EM. Taken together, we describe a rapid and efficient system for the production of large quantities of affinity-purified HCV allowing a comprehensive analysis of the infectious virion, including the determination of its lipid composition.

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Apolipoprotein B: a clinically important apolipoprotein which assembles atherogenic lipoproteins and promotes the development of atherosclerosis

Cited by 258 publications

References 126 publications

Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control

Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control

A proteomic study of serum from children with autism showing differential expression of apolipoproteins and complement proteins

Biochemical and Morphological Properties of Hepatitis C Virus Particles and Determination of Their Lipidome

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