Disease relevance of Apob

• We have previously reported a positive correlation between the expression of BHMT (betaine-homocysteine S-methyltransferase) and ApoB (apolipoprotein B) in rat hepatoma McA (McArdle RH-7777) cells [Sowden, Collins, Smith, Garrow, Sparks and Sparks (1999) Biochem. J. 341, 639-645] [1].
• HIV protease inhibitors protect apolipoprotein B from degradation by the proteasome: a potential mechanism for protease inhibitor-induced hyperlipidemia [2].
• Monomethylethanolamine reduces plasma triacylglycerols and apolipoprotein B and increases apolipoprotein A-I rats without induction of fatty liver [3].
• We have found that, in chylomicrons from intestinal lymph fistulas in the rat, the sole molecular species of apolipoprotein B (apo B) is B-48 [4].
• Moreover, apolipoprotein B extracted from isolated glomeruli of proteinuric passive Heymann nephritis rats shows degradation and lipid peroxidation adduct formation, similar to apoproteins of oxidized lipoproteins in atherosclerotic lesions [5].

High impact information on Apob

• A novel form of RNA editing generates two forms of apolipoprotein B (apo-B) mRNA by converting C at nucleotide 6666 to U or a U-like base [6].
• Unexpectedly, protease inhibitors also inhibited the secretion of apolipoprotein B. This was associated with inhibition of cholesteryl-ester synthesis and microsomal triglyceride transfer-protein activity [2].
• Using cultured human and rat hepatoma cells and primary hepatocytes from transgenic mice, we demonstrate that protease inhibitor treatment inhibits proteasomal degradation of nascent apolipoprotein B, the principal protein component of triglyceride and cholesterol-rich plasma lipoproteins [2].
• Indirect immunofluorescence techniques were employed to determine the distribution within intestinal epithelial cells of apolipoprotein B, a protein essential for the normal transport of fat [7].
• This study demonstrates the presence of apolipoprotein B within intestinal epithelium and provides evidence for the participation of this apoprotein in intestinal lipid transport [7].

Chemical compound and disease context of Apob

• Oleate-mediated stimulation of apolipoprotein B secretion from rat hepatoma cells. A function of the ability of apolipoprotein B to direct lipoprotein assembly and escape presecretory degradation [8].
• CONCLUSION: This study is the first to show that high-fat enteral nutrition, leading to increased plasma triacylglycerol and apolipoprotein B levels, significantly decreases endotoxemia and bacterial translocation after hemorrhage [9].
• Age-related response to dietary fructose in the rat: discrepancy in triglyceride and apolipoprotein B synthesis as a possible mechanism for fatty liver induction in adult rats [10].
• Suppression of the protein tyrosine phosphatase LAR reduces apolipoprotein B secretion by McA-RH7777 rat hepatoma cells [11].
• In this study, we investigated the effects of vitamin E and vitamin C on plasma lipid peroxidation and the susceptibility of apolipoprotein B (apo B)-containing lipoproteins to oxidation in experimental hyperthyroidism [12].

Biological context of Apob

• Lipid peroxidation and oxidant stress regulate hepatic apolipoprotein B degradation and VLDL production [13].
• Two novel mRNA transcripts have been identified that result from species- and tissue-specific, alternative polyadenylation and splicing of the pre-mRNA encoding the apolipoprotein B (apoB) editing catalytic subunit 1 (APOBEC-1) complementation factor (ACF) family of related proteins [14].
• Apolipoprotein B messenger RNA editing in the rat liver. Modulation by fasting and refeeding a high carbohydrate diet [15].
• C to U editing of apolipoprotein B (apoB) mRNA involves the interaction of a multicomponent editing enzyme complex with a requisite RNA sequence embedded within an AU-rich context [16].
• Coordinate regulation of lipogenesis, the assembly and secretion of apolipoprotein B-containing lipoproteins by sterol response element binding protein 1 [17].

Anatomical context of Apob

• Apolipoprotein B mRNA editing is developmentally regulated in the human and rodent small intestine, changing from <1% at day 14 to approximately 90% by day 20 in the rat fetus [18].
• Utilizing small intestine isografts implanted into the subcutaneous tissue of adult recipients, apolipoprotein B mRNA editing was developmentally up-regulated, parallel to that seen with an intact control [18].
• The newly formed apolipoprotein B in very-low-density lipoproteins secreted by the isolated liver and by the primary culture hepatocytes of suckling rats was predominantly a high-molecular-weight form [19].
• Secretion of apolipoprotein B-containing lipoproteins from HeLa cells is dependent on expression of the microsomal triglyceride transfer protein and is regulated by lipid availability [20].
• The microsomal triglyceride transfer protein facilitates assembly and secretion of apolipoprotein B-containing lipoproteins and decreases cotranslational degradation of apolipoprotein B in transfected COS-7 cells [21].

Associations of Apob with chemical compounds

• Thyroid hormone modulates the introduction of a stop codon in rat liver apolipoprotein B messenger RNA [22].
• Microsomal triglyceride transfer protein (MTP), a heterodimer of 97 kDa and protein disulfide isomerase, is required for the assembly of apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins [23].
• Induction of cytidine to uridine editing on cytoplasmic apolipoprotein B mRNA by overexpressing APOBEC-1 [24].
• Normal activity of microsomal triglyceride transfer protein is required for the oleate-induced secretion of very low density lipoproteins containing apolipoprotein B from McA-RH7777 cells [25].
• Apolipoprotein B (apoB) mRNA is modified by a posttranscriptional editing reaction in which a single base (C to U) change in apoB100 mRNA modifies a glutamine (CAA) to a translational stop codon (UAA), producing apoB48 mRNA in mammalian intestine [15].

Physical interactions of Apob

• Apolipoprotein B binding to microsomal triglyceride transfer protein decreases with increases in length and lipidation: implications in lipoprotein biosynthesis [23].
• Apolipoprotein B-editing complex catalytic subunit 1 (APOBEC1) is the catalytic component of an RNA-editing complex that deaminates C6666 --> U in apolipoprotein B RNA in gastrointestinal tissue, thereby generating a premature stop codon [26].
• The salvaged cholesterol could then be transported to neurons by apolipoprotein E-complexes and taken up via the apolipoprotein E/apolipoprotein B (low-density lipoprotein) receptor [27].
• Analysis of biliary 99mTc activity provided evidence for the excretion of 99mTc-labelled apolipoprotein B. The amount of biliary excreted protein-bound 99mTc was linked to total hepatic 99mTc-LDL uptake and presumably reflected LDL receptor-mediated apolipoprotein excretion [28].

Enzymatic interactions of Apob

• Apobec-1 catalyzes C to U editing of apolipoprotein B (apoB) mRNA in the mammalian intestine [29].

Regulatory relationships of Apob

• Inhibition of the microsomal triglyceride transfer protein blocks the first step of apolipoprotein B lipoprotein assembly but not the addition of bulk core lipids in the second step [30].

Other interactions of Apob

• Identification of novel alternative splice variants of APOBEC-1 complementation factor with different capacities to support apolipoprotein B mRNA editing [14].
• Developmental regulation of apolipoprotein B mRNA editing is an autonomous function of small intestine involving homeobox gene Cdx1 [18].
• Concentrations of apolipoprotein A-IV and the high-molecular-weight form of apolipoprotein B were markedly high during the early suckling periods and decreased at weaning [19].
• In ovariectomized controls, estradiol reduced plasma LDL cholesterol, apolipoprotein B, and fibrinogen and increased apolipoprotein A-I and triglycerides [31].
• The production of apolipoprotein B (apo B), apolipoprotein E (apo E), albumin, and transferrin was determined by immunoprecipitation [32].

Analytical, diagnostic and therapeutic context of Apob

• Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA [33].
• During lipid absorption in normal rats, an early and sustained increase in immunofluorescence was demonstrated, consistent with an increase synthesis of apolipoprotein B during lipid absorption [7].
• The technique was then used with flow cytometry of single-cell suspensions of control rat hepatocytes derived from immunostained primary cultures to reveal cell-to-cell heterogeneity of apolipoprotein B epitope expression manifested as apolipoprotein B-negative and positive populations [34].
• Upon addition to LDL, Tris-Gal-Chol was immediately incorporated, and after intravenous injection into rats, the iodine-labeled apolipoprotein B radioactivity was readily associated with the liver [35].
• Here we have localized by immunocytochemistry rat apolipoprotein E and apolipoprotein B within subepithelial immune deposits [5].

References