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Methods in Enzymology 1996
Topics: Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Blood Proteins; Centrifugation, Density Gradient; Densitometry; Electrophoresis, Polyacrylamide Gel; Humans; Lipoproteins, LDL; Reference Standards; Sodium Dodecyl Sulfate; Ultracentrifugation
PubMed: 8749002
DOI: 10.1016/s0076-6879(96)63007-9 -
Lancet (London, England) May 1988
Topics: Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Arteriosclerosis; Humans; Lipid Metabolism; Receptors, LDL
PubMed: 2896961
DOI: No ID Found -
Journal of Lipid Research Jul 1994The present work describes a procedure for determining apolipoproteins (apo) B-100 and B-48 in subfractions of triglyceride-rich lipoproteins by analytical sodium...
The present work describes a procedure for determining apolipoproteins (apo) B-100 and B-48 in subfractions of triglyceride-rich lipoproteins by analytical sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) with Coomassie staining. The chromogenicity of the two apoB species was found to be almost equal, and independent of lipoprotein particle size. Both proteins were sensitive to overloading of the gel, which resulted in low dye uptake. This was particularly evident for apoB-48. The precision of this analytical SDS-PAGE-based procedure to determine the plasma concentrations of apoB-100 and B-48 in triglyceride-rich lipoproteins was found to be appreciably low (coefficients of variation ranging between 3.1 and 14.1%).
Topics: Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Electrophoresis, Polyacrylamide Gel; Evaluation Studies as Topic; Humans; Lipoproteins; Reproducibility of Results; Sensitivity and Specificity; Triglycerides
PubMed: 7964192
DOI: No ID Found -
Circulation Nov 1990For the past 5 years, investigators from many different laboratories have contributed to a greatly increased understanding of two very important lipid-carrying proteins... (Review)
Review
For the past 5 years, investigators from many different laboratories have contributed to a greatly increased understanding of two very important lipid-carrying proteins in plasma--apo B-100 and apo B-48. Apo B-100, an extremely large protein composed of 4,536 amino acids, is synthesized by the liver and is crucial for the assembly of triglyceride-rich VLDL particles. Apo B-100 is virtually the only protein of LDL, a cholesteryl ester-enriched class of lipoproteins that are metabolic products of VLDL. The apo B-100 of LDL serves as a ligand for the LDL receptor-mediated uptake of LDL particles by the liver and extrahepatic tissues. The LDL receptor-binding region of apo B-100 is located in the carboxyterminal portion of the molecule, whereas its lipid-binding regions appear to be broadly dispersed throughout its length. Apo B-48 contains the amino-terminal 2,152 amino acids of apo B-100 and is produced by the intestine as a result of editing of a single nucleotide of the apo B mRNA, which changes the codon specifying apo B-100 amino acid 2,153 to a premature stop codon. Apo B-48 has an obligatory structural role in the formation of chylomicrons; therefore, its synthesis is essential for absorption of dietary fats and fat-soluble vitamins. Both apo B-48 and apo B-100 are encoded on chromosome 2 by a single gene that contains 29 exons and 28 introns. An elevated level of apo B-100 in the plasma is a potent risk factor for developing premature atherosclerotic disease. In the past 3 years, many different apo B gene mutations that affect the concentrations of both apo B and cholesterol in the plasma have been characterized. A missense mutation in the codon for apo B-100 amino aid 3,500 is associated with hypercholesterolemia. This mutation results in poor binding of apo B-100 to the LDL receptor, thereby causing the cholesteryl ester-enriched LDL particles to accumulate in the plasma. This disorder is called familial defective apo B-100, and it is probably a cause of premature atherosclerotic disease. Familial hypobetalipoproteinemia is a condition associated with abnormally low levels of apo B and cholesterol; affected individuals may actually have a reduced risk of atherosclerotic disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Topics: Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Cholesterol; Genetic Variation; Humans; Hyperlipoproteinemias; Hypolipoproteinemias; Mutation; Polymorphism, Restriction Fragment Length
PubMed: 1977530
DOI: 10.1161/01.cir.82.5.1574 -
Nihon Rinsho. Japanese Journal of... Sep 1999
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Trends in Cardiovascular Medicine 1999It generally is assumed that lipoproteins containing apolipoprotein B (apo B) are secreted only by the intestine and the liver. However, we recently demonstrated that... (Review)
Review
It generally is assumed that lipoproteins containing apolipoprotein B (apo B) are secreted only by the intestine and the liver. However, we recently demonstrated that the human apo-B gene also is expressed in the hearts of human apo-B transgenic mice and in human heart tissue. Using metabolic labeling techniques, we showed that heart tissue from human apo-B transgenic mice and nontransgenic mice, as well as human heart tissue, synthesize and secrete apo-B-containing lipoproteins. The reason why the heart makes lipoproteins is unknown, but we hypothesized that the heart may use lipoprotein synthesis to unload surplus cellular lipids, particularly triglycerides, which are not immediately required for mitochondrial beta-oxidation.
Topics: Animals; Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Biomarkers; Cells, Cultured; Gene Expression; Golgi Apparatus; Heart; Humans; Lipoproteins; Mice; Mice, Transgenic; Myocardium
PubMed: 10578525
DOI: 10.1016/s1050-1738(99)00011-0 -
Frontiers of Hormone Research 1999
Review
Topics: APOBEC-1 Deaminase; Amino Acid Sequence; Animals; Apolipoproteins B; Binding Sites; Cytidine Deaminase; Humans; Molecular Sequence Data; Molecular Structure; Neoplasms; RNA Editing; RNA, Messenger
PubMed: 10941404
DOI: 10.1159/000060998 -
Journal of Lipid Research Oct 1990Apolipoprotein B (apoB), an apolipoprotein associated with very low density lipoproteins and the atherogenic low density lipoproteins (LDL), directs the metabolism of...
Apolipoprotein B (apoB), an apolipoprotein associated with very low density lipoproteins and the atherogenic low density lipoproteins (LDL), directs the metabolism of lipoprotein particles in plasma by interacting with the LDL receptor. Utilizing human intestinal biopsy organ cultures, we have studied the synthesis of intestinal apoB in man. Intestinal organ cultures from normal adults (n = 6) were incubated in the presence of protease inhibitors in media supplemented with [35S]methionine. Media from these cultures were evaluated by sequential NaDodSO4 polyacrylamide gel electrophoresis, radioautography, and Western blot analyses, and intestinal biopsies were studied using immunohistochemistry. The relative abundance of apoB-100 and apoB-48 mRNA was assessed using reverse transcriptase-polymerase chain reaction followed by primer extension. Although apoB-48 was the principal isoprotein that was newly synthesized by intestinal organ cultures, apoB-100 was also synthesized and secreted by human intestinal organ cultures with 16 +/- 3% of the intestinal apoB mRNA coding for apoB-100. These results establish that apoB-100 is produced by the human intestine. The synthesis of the atherogenic apoB-100 by the intestine has pathophysiologic implications for the development of diet-induced atherosclerosis.
Topics: Adult; Apolipoprotein B-100; Apolipoprotein B-48; Apolipoproteins B; Base Sequence; Blotting, Western; Electrophoresis, Polyacrylamide Gel; Humans; Immunohistochemistry; Intestinal Mucosa; Molecular Sequence Data; Organ Culture Techniques; Protease Inhibitors; RNA, Messenger
PubMed: 2079601
DOI: No ID Found -
Reviews in Endocrine & Metabolic... Dec 2004
Review
Topics: Animals; Apolipoproteins B; Biological Transport; Carrier Proteins; Gene Expression Regulation; Homeostasis; Humans; Insulin Resistance; Lipids; Lipoproteins, VLDL; Liver; Molecular Chaperones; Protein Biosynthesis; Signal Transduction
PubMed: 15486461
DOI: 10.1023/B:REMD.0000045100.66675.92 -
Current Opinion in Lipidology Jun 2005Apolipoprotein B-containing lipoprotein assembly and secretion is critical for lipid absorption and triglyceride homeostasis, and plays a role in atherogenesis and the... (Review)
Review
PURPOSE OF REVIEW
Apolipoprotein B-containing lipoprotein assembly and secretion is critical for lipid absorption and triglyceride homeostasis, and plays a role in atherogenesis and the pathobiology of type 2 diabetes and obesity. This review highlights recent insights into the evolutionary, structural, and cell biology of hepatic and intestinal pathways for lipid mobilization, and the mechanisms and regulation of lipoprotein assembly and secretion.
RECENT FINDINGS
Until recently it was assumed that microsomal triglyceride transfer protein-dependent apolipoprotein B-containing lipoprotein assembly was a unique adaptation associated with vertebrate lipid homeostasis. However, it is now clear that microsomal triglyceride transfer protein (MTP) exists in species whose last common ancestor diverged over 550 million years ago. In its long evolutionary history, the MTP gene has given rise to a series of paralogous lipid transport proteins, all of which require MTP for their biogenesis. During its evolution, MTP has acquired new functions, enabling it to participate in a disparate array of lipid mobilization and transport pathways, ranging from primitive lipoprotein assembly to antigenic lipid presentation. In addition to the complex and multifunctional role of MTP in apolipoprotein B assembly, other factors responsible for the generation of secretion-coupled lipids and the modulation of apolipoprotein B production are emerging.
SUMMARY
The phylogenic dissection of MTP and apolipoprotein B function, coupled with ongoing structural and biochemical analyses, provide significant insights into the mechanisms of lipid mobilization and secretion. Some of these factors and processes may be targeted therapeutically to modulate the quantitative and qualitative aspects of apolipoprotein B production.
Topics: Apolipoproteins B; Carrier Proteins; Evolution, Molecular; Homeostasis; Humans; Lipid Metabolism; Microsomes; Triglycerides
PubMed: 15891394
DOI: 10.1097/01.mol.0000169353.12772.eb