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The Journal of Biological Chemistry May 2002
Review
Topics: Animals; Apolipoproteins B; Endoplasmic Reticulum; Humans; Lipoproteins; Liver; Models, Molecular; Protein Processing, Post-Translational
PubMed: 12006608
DOI: 10.1074/jbc.R100068200 -
Journal of Internal Medicine Nov 2005Apolipoprotein (apo) B exists in two forms apoB100 and apoB48. ApoB100 is present on very low-density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and... (Review)
Review
Apolipoprotein (apo) B exists in two forms apoB100 and apoB48. ApoB100 is present on very low-density lipoproteins (VLDL), intermediate density lipoproteins (IDL) and LDL. ApoB100 assembles VLDL particles in the liver. This process starts by the formation of a pre-VLDL, which is retained in the cell unless converted to the triglyceride-poor VLDL2. VLDL2 is secreted or converted to VLDL1 by a bulk lipidation in the Golgi apparatus. ApoB100 has a central role in the development of atherosclerosis. Two proteoglycan-binding sequences in apoB100 have been identified, which are important for retaining the lipoprotein in the intima of the artery. Retention is essential for the development of the atherosclerotic lesion.
Topics: Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Glycosaminoglycans; Humans; Hyperlipidemias; Lipoproteins, VLDL; Models, Biological; Proteoglycans; Risk Factors; Triglycerides
PubMed: 16238675
DOI: 10.1111/j.1365-2796.2005.01556.x -
The Journal of Clinical Investigation Dec 1993The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants,...
The B apolipoproteins, apo-B48 and apo-B100, are key structural proteins in those classes of lipoproteins considered to be atherogenic [e.g., chylomicron remnants, beta-VLDL, LDL, oxidized LDL, and Lp(a)]. Here we describe the development of transgenic mice expressing high levels of human apo-B48 and apo-B100. A 79.5-kb human genomic DNA fragment containing the entire human apo-B gene was isolated from a P1 bacteriophage library and microinjected into fertilized mouse eggs. 16 transgenic founders expressing human apo-B were generated, and the animals with the highest expression had plasma apo-B100 levels nearly as high as those of normolipidemic humans (approximately 50 mg/dl). The human apo-B100 in transgenic mouse plasma was present largely in lipoproteins of the LDL class as shown by agarose gel electrophoresis, chromatography on a Superose 6 column, and density gradient ultracentrifugation. When the human apo-B transgenic founders were crossed with transgenic mice expressing human apo(a), the offspring that expressed both transgenes had high plasma levels of human Lp(a). Both the human apo-B and Lp(a) transgenic mice will be valuable resources for studying apo-B metabolism and the role of apo-B and Lp(a) in atherosclerosis.
Topics: Animals; Apolipoprotein B-100; Apolipoproteins B; Base Sequence; Blotting, Southern; DNA; DNA Primers; Electrophoresis, Agar Gel; Female; Humans; Immunoblotting; Lipoprotein(a); Lipoproteins; Male; Mice; Mice, Transgenic; Microinjections; Molecular Sequence Data; Polymerase Chain Reaction; Restriction Mapping; Transcription, Genetic
PubMed: 8254057
DOI: 10.1172/JCI116927 -
BMC Genomics Dec 2022In the late phase of production, ducks untimely cease laying, leading to a lower feed conversion. Liver plays a vital role in the synthesis and transport of yolk...
BACKGROUND
In the late phase of production, ducks untimely cease laying, leading to a lower feed conversion. Liver plays a vital role in the synthesis and transport of yolk materials during egg formation in birds. However, the molecular mechanism of liver in ceased-laying duck is far from clear, higher resolution and deeper analysis is needed. Sing-cell RNA-sequencing of 10 × Genomics platform can help to map the liver single cell gene expression atlas of Shaoxing duck and provide new insights into the liver between egg-laying and ceased-laying ducks.
RESULTS
About 20,000 single cells were profiled and 22 clusters were identified. All the clusters were identified as 6 cell types. The dominant cell type is hepatocyte, accounted for about 60% of all the cells. Of note, the heterogeneity of cells between egg-laying duck and ceased-laying duck mainly occurred in hepatocytes. Cells of cluster 3 and 12 were the unique hepatocyte states of egg-laying ducks, while cells of cluster 0 and 15 were the unique hepatocyte states of ceased-laying ducks. The expression mode of yolk precursor transporters, lipid metabolizing enzymes and fibrinogens were different in hepatocytes between egg-laying duck and ceased-laying duck. APOV1, VTG2, VTG1, APOB, RBP, VTDB and SCD might be activated in egg-laying ducks, while APOA1, APOA4, APOC3, FGB and FGG might be activated in ceased-laying ducks.
CONCLUSIONS
Our study further proofs that APOV1 and APOB play key roles in egg production, rather than APOA1 and APOA4. It is also the first to detect a correlation between the higher expression of APOC3, FGB, FGG and ceased-laying in duck.
Topics: Animals; Ducks; Liver; Oviposition; Carrier Proteins; Sequence Analysis, RNA; Apolipoproteins B; Reproduction
PubMed: 36577943
DOI: 10.1186/s12864-022-09089-0 -
Journal of Hepatology Sep 2009
Topics: Adenylate Kinase; Animals; Apolipoproteins B; Dietary Fats; Disease Models, Animal; Disease Progression; Fatty Liver; Humans; Lipogenesis; Mice; Mice, Transgenic; Smoking; Sterol Regulatory Element Binding Protein 1; Tobacco Smoke Pollution
PubMed: 19596475
DOI: 10.1016/j.jhep.2009.05.021 -
The Biochemical Journal Nov 1992Non-esterified fatty acids (NEFAs) and insulin are important factors in the control of lipoprotein secretion, but the mechanism of action is unclear. The present study...
Non-esterified fatty acids (NEFAs) and insulin are important factors in the control of lipoprotein secretion, but the mechanism of action is unclear. The present study was undertaken to determine whether insulin and NEFAs modulated hepatic secretion of triacylglycerol and apolipoprotein B (apo-B) by regulation of hepatic intracellular apo-B content. The experiments were performed with the human hepatoblastoma cell line Hep G2, for periods of up to 72 h in the presence and absence of NEFAs and insulin. Higher concentrations of eicosapentanoate (EPA) sustained for 72 h decreased cellular protein content (at 250 microM) or caused cell death (at 750 microM), and this effect was not observed with the other NEFAs studied, whereas 75 microM-EPA did not affect cell viability. Compared with the absence of NEFA, 75 microM-EPA did not alter the intracellular triacylglycerol content, but decreased the intracellular content of apo-B by 47% (P < 0.01) and decreased secreted triacylglycerol and secreted apo-B by 13% (P < 0.05) and 21% (P < 0.01) respectively, after 72 h. However 250 microM-oleate increased the intracellular triacylglycerol by 36% (P < 0.01), intracellular apo-B by 22% (P < 0.05) and secreted triacylglycerol and apo-B by 20-30% (P < 0.05-0.01). Insulin decreased secreted triacylglycerol and apo-B in the presence of each NEFA studied by 20-30%. There was no correlation between the changes in intracellular triacylglycerol and the rate of secretion. However, when the secreted triacylglycerol or apo-B was plotted against intracellular apo-B content a significant correlation was observed (r = 0.89, P < 0.001 for both analyses). Apo-B mRNA levels did not change after 72 h incubation with oleate or EPA. These results demonstrate that EPA can be toxic to hepatocytes and that NEFAs and insulin control secretion of triacylglycerol and apo-B by regulation of the intracellular apo-B concentration, thus controlling assembly of apo-B with triacylglycerol to form lipoproteins.
Topics: Apolipoproteins B; Carcinoma, Hepatocellular; Cell Death; Eicosapentaenoic Acid; Fatty Acids, Nonesterified; Humans; Insulin; Kinetics; Liver Neoplasms; Oleic Acid; Oleic Acids; RNA, Messenger; Regression Analysis; Triglycerides; Tumor Cells, Cultured
PubMed: 1332692
DOI: 10.1042/bj2880101 -
Analytical Biochemistry May 1995Numerous reports indicate that the oxidation of low-density lipoprotein (LDL) can significantly change its metabolic and physiological properties. Most methods for...
Numerous reports indicate that the oxidation of low-density lipoprotein (LDL) can significantly change its metabolic and physiological properties. Most methods for evaluation of LDL oxidation require isolation of lipoprotein, making the procedure laborious and increasing the probability of artifactual modification of LDL. In this paper we describe an immunochemical approach which can be used to measure the oxidation of isolated LDL and apoprotein B in unfractionated serum and to evaluate the effects of antioxidants on these processes. The procedure is based on differential recognition by monoclonal antibodies of native and oxidized lipoproteins. The results obtained with our assay indicate a strong correlation between the changes of apo B epitope expression during oxidation and the formation of conjugated dienes, changes in lipoprotein electrophoretic mobility, and interaction with fibroblast and macrophage receptors. The sensitivity of apo B to oxidation varies greatly among serum samples obtained from individual donors. These differences do not correlate with the differences in sensitivity to oxidation of LDL isolated from the blood samples of the same donors. It is also shown that apo B oxidation in serum can be progressively inhibited in the presence of increasing amounts of various antioxidants.
Topics: Animals; Antibodies, Monoclonal; Antigen-Antibody Reactions; Antioxidants; Apolipoproteins B; Cell Line; Copper; Copper Sulfate; Endocytosis; Epitopes; Female; Humans; Immunoassay; Kinetics; Lipoproteins, LDL; Male; Malondialdehyde; Mice; Mice, Inbred BALB C; Oxidation-Reduction; Time Factors
PubMed: 7545355
DOI: 10.1006/abio.1995.1274 -
The Journal of Biological Chemistry Aug 2003Apolipoprotein B is secreted with atherogenic lipids as lipoprotein particles from hepatocytes. Regulation of the secretion of apolipoprotein B is largely...
Apolipoprotein B is secreted with atherogenic lipids as lipoprotein particles from hepatocytes. Regulation of the secretion of apolipoprotein B is largely post-translational and reflects the balance between processes that leads to particle assembly or to intracellular degradation. Previously, we conducted a proteomic screen to find proteins that bind apolipoprotein B in rat liver microsomes. We identified ferritin heavy and light chains in this screen among other proteins and showed that the two ferritins bind apolipoprotein B directly in vitro. In hepatocytes and other cells, ferritin heavy and light chains form cytosolic cages that store iron. We now show that ferritin heavy or light chains post-translationally inhibit the secretion of apolipoprotein B without altering the export of other hepatic proteins including albumin, factor XIII, and apolipoprotein A-I. This inhibition of apolipoprotein B secretion is not due to diminished lipid synthesis and can be partially overcome by stimulating triglyceride synthesis. The block in apolipoprotein B secretion by ferritins leads to an increase in endoplasmic reticulum-associated degradation of the apolipoprotein. Thus, despite being cytosolic proteins without known chaperone activity, ferritins can specifically regulate the secretion of apolipoprotein B post-translationally. The metabolic pathways for iron storage and intercellular cholesterol and triglyceride transport could intersect.
Topics: Apolipoproteins B; Base Sequence; Cell Line; DNA Primers; Ferritins; Humans; Protein Processing, Post-Translational
PubMed: 12813058
DOI: 10.1074/jbc.M303081200 -
Journal of Lipid Research Aug 2006Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production,... (Review)
Review
Lipoprotein metabolism is the result of a complex network of many individual components. Abnormal lipoprotein concentrations can result from changes in the production, conversion, or catabolism of lipoprotein particles. Studies in hypolipoproteinemia and hyperlipoproteinemia have elucidated the processes that control VLDL secretion as well as VLDL and LDL catabolism. Here, we review the current knowledge regarding apolipoprotein B (apoB) metabolism, focusing on selected clinically relevant conditions. In hypobetalipoproteinemia attributable to truncations in apoB, the rate of secretion is closely linked to the length of apoB. On the other hand, in patients with the metabolic syndrome, it appears that substrate, in the form of free fatty acids, coupled to the state of insulin resistance can induce hypersecretion of VLDL-apoB. Studies in patients with familial hypercholesterolemia, familial defective apoB, and mutant forms of proprotein convertase subtilisin/kexin type 9 show that mutations in the LDL receptor, the ligand for the receptor, or an intracellular chaperone for the receptor are the most important determinants in regulating LDL catabolism. This review also demonstrates the variance of results within similar, or even the same, phenotypic conditions. This underscores the sensitivity of metabolic studies to methodological aspects and thus the importance of the inclusion of adequate controls in studies.
Topics: Apolipoproteins B; Humans; Kinetics; Lipid Metabolism; Lipoproteins, LDL; Lipoproteins, VLDL; Metabolic Diseases; Models, Biological
PubMed: 16720894
DOI: 10.1194/jlr.R600013-JLR200 -
European Journal of Biochemistry Dec 1995In this study we have characterized four of the principle goose apolipoproteins and compared their physicochemical properties with human and avian counterparts. Goose...
In this study we have characterized four of the principle goose apolipoproteins and compared their physicochemical properties with human and avian counterparts. Goose ApoB-100 and ApoAI amino acid compositions were very similar to their chicken and human homologous proteins. The partial N-terminal sequence from goose ApoAI was 91% and 82% similar to the corresponding duck and chicken proteins, respectively. Most of the observed amino acid changes detected between the ApoAI sequences were amino acid replacements having the same characteristics and could be the result of a single base mutation. The N-terminal portion of two ApoC-like apolipoproteins were also studied. Goose ApoCa had an electrophoretic mobility of 0.31 and exhibited a nine-residue motif that was well conserved between ApoCIII sequences from different species. We therefore suggest that ApoCa is the equivalent of mammalian ApoCIII. The N-terminal portion of goose ApoCb, the second major ApoC in high-density apolipoprotein, showed no similarity to proteins previously described in the literature. This protein displayed two isomorphs in alkaline urea gel electrophoresis called ApoCb1 and ApoCb2 with Rf values of 0.36 and 0.39, respectively. A genetic polymorphism was detected in the population whereby 25% of the animals carried only one isomorph and 50% exhibited both ApoCb isomorphs. These frequencies were similar in females and males. The transmission mode of these ApoCb isomorphs was consistent with two segregating alleles from a single codominantly expressed gene.
Topics: Amino Acid Sequence; Animals; Apolipoprotein A-I; Apolipoprotein B-100; Apolipoproteins B; Apolipoproteins C; Electrophoresis; Female; Geese; Humans; Male; Molecular Sequence Data; Polymorphism, Genetic
PubMed: 8536707
DOI: 10.1111/j.1432-1033.1995.586_b.x