Skip to main content
SpringerLink
Log in

Inhibition of the Synthesis of Apolipoprotein B-Containing Lipoproteins

  • Chapter
Atherosclerosis: Diet and Drugs

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 170))

Abstract

Increased serum concentrations of low density lipoproteins represent a major cardiovascular risk factor. Low-density lipoproteins are derived from very low density lipoproteins secreted by the liver. Apolipoprotein (apo)B that constitutes the essential structural protein of these lipoproteins exists in two forms, the full length form apoB-100 and the carboxy-terminal truncated apoB-48. The generation of apoB-48 is due to editing of the apoB mRNA which generates a premature stop translation codon. The editing of apoB mRNA is an important regulatory event because apoB-48-containing lipoproteins cannot be converted into the atherogenic low density lipoproteins. The apoB gene is constitutively expressed in liver and intestine, and the rate of apoB secretion is regulated post-transcriptionally. The translocation of apoB into the endoplasmic reticulum is complicated by the hydrophobicity of the nascent polypeptide. The assembly and secretion of apoB-containing lipoproteins within the endoplasmic reticulum is strictly dependent on the microsomal tricylceride transfer protein which shuttles triglycerides onto the nascent lipoprotein particle. The overall synthesis of apoB lipoproteins is regulated by proteosomal and nonproteosomal degradation and is dependent on triglyceride availability. Noninsulin dependent diabetes mellitus, obesity and the metabolic syndrome are characterized by an increased hepatic synthesis of apoB-containing lipoproteins. Interventions aimed to reduce the hepatic secretion of apoB-containing lipoproteins are therefore of great clinical importance. Lead targets in these pathways are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 429.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 549.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adeli K, Macri J, Mohammadi A, Kito M, Urade R, Cavallo D (1997) Apolipoprotein B is intracellularly associated with an ER-60 protease homologue in HepG2 cells. J Biol Chem 272:22489–22494

    Article  PubMed  Google Scholar 

  • Aguilar-Salinas CA, Barrett PH, Parhofer KG, Young SG, Tessereau D, Bateman J, Quinn C, Schonfeld G (1995) Apoprotein B-100 production is decreased in subjects heterozygous for truncations of apoprotein B. Arterioscler Thromb Vasc Biol 15:71–80

    PubMed  Google Scholar 

  • Ameen C, Oscarsson J (2003) Sex difference in hepatic microsomal triglyceride transfer protein expression is determined by the growth hormone secretory pattern in the rat. Endocrinology 144:3914–3921

    Article  PubMed  Google Scholar 

  • Antes TJ, Goodart SA, Huynh C, Sullivan M, Young SG, Levy-Wilson B (2000) Identification and characterization of a 315-base pair enhancer, located more than 55 kilobases 5′ of the apolipoprotein B gene, that confers expression in the intestine. J Biol Chem 275:26637–26648

    Article  PubMed  Google Scholar 

  • Arakawa H, Hauschild J, Buerstedde JM (2002) Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion. Science 295:1301–1306

    Article  PubMed  Google Scholar 

  • Au WS, Kung HF, Lin MC (2003) Regulation of microsomal triglyceride transfer protein gene by insulin in HepG2 cells: roles of MAPKerk and MAPKp38. Diabetes 52:1073–1080

    PubMed  Google Scholar 

  • Bartels ED, Lauritsen M, Nielsen LB (2002) Hepatic expression of microsomal triglyceride transfer protein and in vivo secretion of triglyceride-rich lipoproteins are increased in obese diabetic mice. Diabetes 51:1233–1239

    PubMed  Google Scholar 

  • Baum CL, Teng BB, Davidson NO (1990) Apolipoprotein B messenger RNA editing in the rat liver. Modulation by fasting and refeeding a high carbohydrate diet. J Biol Chem 265:19263–19270

    PubMed  Google Scholar 

  • Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L, Whelton PK (2002) Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Am J Clin Nutr 76:93–99

    PubMed  Google Scholar 

  • Benoist F, Grand-Perret T (1997) Co-translational degradation of apolipoprotein B100 by the proteasome is prevented by microsomal triglyceride transfer protein. Synchronized translation studies on HepG2 cells treated with an inhibitor of microsomal triglyceride transfer protein. J Biol Chem 272:20435–20442

    Article  PubMed  Google Scholar 

  • Blackhart BD, Ludwig EM, Pierotti VR, Caiati L, Onasch MA, Wallis SC, Powell L, Pease R, Knott TJ, Chu ML, et al. (1986) Structure of the human apolipoprotein B gene. J Biol Chem 261:15364–15367

    PubMed  Google Scholar 

  • Blanc V, Henderson JO, Kennedy S, Davidson NO (2001a)Mutagenesis of apobec-1 complementation factor reveals distinct domains that modulate RNA binding, protein-protein interaction with apobec-1, and complementation of C to U RNA-editing activity. J Biol Chem 276:46386–46393

    PubMed  Google Scholar 

  • Blanc V, Kennedy S, Davidson NO (2003) A novel nuclear localization signal in the auxiliary domain of apobec-1 complementation factor regulates nucleocytoplasmic import and shuttling. J Biol Chem 278:41198–41204

    PubMed  Google Scholar 

  • Blanc V, Navaratnam N, Henderson JO, Anant S, Kennedy S, Jarmuz A, Scott J, Davidson NO (2001b) Identification of GRY-RBP as an apolipoprotein B RNA-binding protein that interacts with both apobec-1 and apobec-1 complementation factor to modulate C to U editing. J Biol Chem 276:10272–10283

    Article  PubMed  Google Scholar 

  • Bok SH, Lee SH, Park YB, Bae KH, Son KH, Jeong TS, Choi MS (1999) Plasma and hepatic cholesterol and hepatic activities of 3-hydroxy-3-methyl-glutaryl-CoA reductase and acyl CoA: cholesterol transferase are lower in rats fed citrus peel extract or a mixture of citrus bioflavonoids. J Nutr 129:1182–1185

    PubMed  Google Scholar 

  • Borchardt RA, Davis RA (1987) Intrahepatic assembly of very low density lipoproteins. Rate of transport out of the endoplasmic reticulum determines rate of secretion. J Biol Chem 262:16394–16402

    PubMed  Google Scholar 

  • Boren J, Lee I, Zhu W, Arnold K, Taylor S, Innerarity TL (1998a) Identification of the low density lipoprotein receptor-binding site in apolipoprotein B100 and the modulation of its binding activity by the carboxyl terminus in familial defective apo-B100. J Clin Invest 101:1084–1093

    PubMed  Google Scholar 

  • Boren J, Olin K, Lee I, Chait A, Wight TN, Innerarity TL (1998b) Identification of the principal proteoglycan-binding site in LDL. A single-point mutation in apo-B100 severely affects proteoglycan interaction without affecting LDL receptor binding. J Clin Invest 101:2658–2664

    PubMed  Google Scholar 

  • Boren J, Rustaeus S, Olofsson SO (1994) Studies on the assembly of apolipoprotein B-100-and B-48-containing very low density lipoproteins in McA-RH7777 cells. J Biol Chem 269:25879–25888

    PubMed  Google Scholar 

  • Borradaile NM, de Dreu LE, Barrett PH, Behrsin CD, Huff MW (2003a) Hepatocyte apoB-containing lipoprotein secretion is decreased by the grapefruit flavonoid, naringenin, via inhibition of MTP-mediated microsomal triglyceride accumulation. Biochemistry 42:1283–1291

    PubMed  Google Scholar 

  • Borradaile NM, de Dreu LE, Barrett PH, Huff MW (2002a) Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters. J Lipid Res 43:1544–1554

    Article  PubMed  Google Scholar 

  • Borradaile NM, De Dreu LE, Huff MW (2003b) Inhibition of net HepG2 cell apolipoprotein b secretion by the citrus flavonoid naringenin involves activation of phosphatidylinositol 3-kinase, independent of insulin receptor substrate-1 phosphorylation. Diabetes 52:2554–2561

    PubMed  Google Scholar 

  • Borradaile NM, de Dreu LE, Wilcox LJ, Edwards JY, Huff MW (2002b) Soya phytoestrogens, genistein and daidzein, decrease apolipoprotein B secretion from HepG2 cells through multiple mechanisms. Biochem J 366:531–539

    PubMed  Google Scholar 

  • Bostrom K, Wettesten M, Boren J, Bondjers G, Wiklund O, Olofsson SO (1986) Pulse-chase studies of the synthesis and intracellular transport of apolipoprotein B-100 in Hep G2 cells. J Biol Chem 261:13800–13806

    PubMed  Google Scholar 

  • Bradbury P, Mann CJ, Kochl S, Anderson TA, Chester SA, Hancock JM, Ritchie PJ, Amey J, Harrison GB, Levitt DG, Banaszak LJ, Scott J, Shoulders CC (1999) A common binding site on the microsomal triglyceride transfer protein for apolipoprotein B and protein disulfide isomerase. J Biol Chem 274:3159–3164

    PubMed  Google Scholar 

  • Bransteitter R, Pham P, Scharff MD, Goodman MF (2003) Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase. Proc Natl Acad Sci USA 100:4102–4107

    Article  PubMed  Google Scholar 

  • Brown MS, Goldstein JL (1986) A receptor-mediated pathway for cholesterol homeostasis. Science 232:34–47

    PubMed  Google Scholar 

  • Brunner C, Kraft HG, Utermann G, Muller HJ (1993) Cys4057 of apolipoprotein(a) is essential for lipoprotein(a) assembly. Proc Natl Acad Sci USA 90:11643–11647

    PubMed  Google Scholar 

  • Brunzell JD, Hokanson JE (1999) Dyslipidemia of central obesity and insulin resistance. Diabetes Care 22Suppl 3: C10–C13

    PubMed  Google Scholar 

  • Cardozo C, Wu X, Pan M, Wang H, Fisher EA (2002) The inhibition of microsomal triglyceride transfer protein activity in rat hepatoma cells promotes proteasomal and nonproteasomal degradation of apoprotein b100. Biochemistry 41:10105–10114

    PubMed  Google Scholar 

  • Carpentier A, Taghibiglou C, Leung N, Szeto L, Van Iderstine SC, Uffelman KD, Buckingham R, Adeli K, Lewis GF (2002) Ameliorated hepatic insulin resistance is associated with normalization of microsomal triglyceride transfer protein expression and reduction in very low density lipoprotein assembly and secretion in the fructose-fed hamster. J Biol Chem 277:28795–28802

    Article  PubMed  Google Scholar 

  • Cartwright IJ, Plonne D, Higgins JA (2000) Intracellular events in the assembly of chylomicrons in rabbit enterocytes. J Lipid Res 41:1728–1739

    PubMed  Google Scholar 

  • Chandler CE, Wilder DE, Pettini JL, Savoy YE, Petras SF, Chang G, Vincent J, Harwood HJ, Jr. (2003) CP-346086: an MTP inhibitor that lowers plasma cholesterol and triglycerides in experimental animals and in humans. J Lipid Res 44:1887–1901

    PubMed  Google Scholar 

  • Chang BH, Liao W, Li L, Nakamuta M, Mack D, Chan L (1999) Liver-specific inactivation of the abetalipoproteinemia gene completely abrogates very low density lipoprotein/low density lipoprotein production in a viable conditional knockout mouse. J Biol Chem 274:6051–6055

    Article  PubMed  Google Scholar 

  • Chen SH, Habib G, Yang CY, Gu ZW, Lee BR, Weng SA, Silberman SR, Cai SJ, Deslypere JP, Rosseneu M, et al. (1987) Apolipoprotein B-48 is the product of a messenger RNA with an organ-specific in-frame stop codon. Science 238:363–366

    PubMed  Google Scholar 

  • Chen X, Sparks JD, Yao Z, Fisher EA (1993) Hepatic polysomes that contain apoprotein B mRNA have unusual physical properties. J Biol Chem 268:21007–21013

    PubMed  Google Scholar 

  • Chen Y, Le Caherec F, Chuck SL (1998) Calnexin and other factors that alter translocation affect the rapid binding of ubiquitin to apoB in the Sec61 complex. J Biol Chem 273:11887–11894

    PubMed  Google Scholar 

  • Chester A, Somasekaram A, Tzimina M, Jarmuz A, Gisbourne J, O'Keefe R, Scott J, Navaratnam N (2003) The apolipoprotein B mRNA editing complex performs a multifunctional cycle and suppresses nonsense-mediated decay. EMBO J 22:3971–3982

    PubMed  Google Scholar 

  • Choi JS, Yokozawa T, Oura H (1991) Antihyperlipidemic effect of flavonoids from Prunus davidiana. J Nat Prod 54:218–224

    Article  PubMed  Google Scholar 

  • Chuck SL, Yao Z, Blackhart BD, McCarthy BJ, Lingappa VR (1990) New variation on the translocation of proteins during early biogenesis of apolipoprotein B. Nature 346:382–385

    Article  PubMed  Google Scholar 

  • Collins HL, Sparks CE, Sparks JD (2000) B48 is preferentially translated over B100 in cells with increased endogenous apoB mRNA. Biochem Biophys Res Commun 273:1156–1160

    Article  PubMed  Google Scholar 

  • Dannoura AH, Berriot-Varoqueaux N, Amati P, Abadie V, Verthier N, Schmitz J, Wetterau JR, Samson-Bouma ME, Aggerbeck LP (1999) Anderson's disease: exclusion of apolipoprotein and intracellular lipid transport genes. Arterioscler Thromb Vasc Biol 19:2494–2508

    PubMed  Google Scholar 

  • Davidson NO, Powell LM, Wallis SC, Scott J (1988) Thyroid hormone modulates the introduction of a stop codon in rat liver apolipoprotein B messenger RNA. J Biol Chem 263:13482–13485

    PubMed  Google Scholar 

  • Davidson NO, Shelness GS (2000) APOLIPOPROTEIN B: mRNA editing, lipoprotein assembly, and presecretory degradation. Annu Rev Nutr 20:169–193

    Article  PubMed  Google Scholar 

  • Davis RA, Hui TY (2001) 2000 George Lyman Duff Memorial Lecture: atherosclerosis is a liver disease of the heart. Arterioscler Thromb Vasc Biol 21:887–898

    PubMed  Google Scholar 

  • Davis RA, Thrift RN, Wu CC, Howell KE (1990) Apolipoprotein B is both integrated into and translocated across the endoplasmic reticulum membrane. Evidence for two functionally distinct pools. J Biol Chem 265:10005–10011

    PubMed  Google Scholar 

  • Demmer LA, Levin MS, Elovson J, Reuben MA, Lusis AJ, Gordon JI (1986) Tissue-specific expression and developmental regulation of the rat apolipoprotein B gene. Proc Natl Acad Sci USA 83:8102–8106

    PubMed  Google Scholar 

  • Di Noia J, Neuberger MS (2002) Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase. Nature 419:43–48

    Article  PubMed  Google Scholar 

  • Dickerson SK, Market E, Besmer E, Papavasiliou FN (2003) AID mediates hypermutation by deaminating single stranded DNA. J Exp Med 197:1291–1296

    Article  PubMed  Google Scholar 

  • Elam MB, Wilcox HG, Solomon SS, Heimberg M (1992) In vivo growth hormone treatment stimulates secretion of very low density lipoprotein by the isolated perfused rat liver. Endocrinology 131:2717–2722

    Article  PubMed  Google Scholar 

  • Ellgaard L, Molinari M, Helenius A (1999) Setting the standards: quality control in the secretory pathway. Science 286:1882–1888

    Article  PubMed  Google Scholar 

  • Fisher EA, Ginsberg HN (2002) Complexity in the secretory pathway: the assembly and secretion of apolipoprotein B-containing lipoproteins. J Biol Chem 277:17377–17380

    Article  PubMed  Google Scholar 

  • Fisher EA, Pan M, Chen X, Wu X, Wang H, Jamil H, Sparks JD, Williams KJ (2001) The triple threat to nascent apolipoprotein B. Evidence for multiple, distinct degradative pathways. J Biol Chem 276:27855–27863

    PubMed  Google Scholar 

  • Fisher EA, Zhou M, Mitchell DM, Wu X, Omura S, Wang H, Goldberg AL, Ginsberg HN (1997) The degradation of apolipoprotein B100 is mediated by the ubiquitin-proteasome pathway and involves heat shock protein 70. J Biol Chem 272:20427–20434

    Article  PubMed  Google Scholar 

  • Fleming JF, Spitsen GM, Hui TY, Olivier L, Du EZ, Raabe M, Davis RA (1999) Chinese hamster ovary cells require the coexpression of microsomal triglyceride transfer protein and cholesterol 7alpha-hydroxylase for the assembly and secretion of apolipoprotein B-containing lipoproteins. J Biol Chem 274:9509–9514

    Article  PubMed  Google Scholar 

  • Fujino T, Navaratnam N, Scott J (1998) Human apolipoprotein B RNA editing deaminase gene (APOBEC1). Genomics 47:266–275

    Article  PubMed  Google Scholar 

  • Funahashi T, Giannoni F, DePaoli AM, Skarosi SF, Davidson NO (1995) Tissue-specific, developmental and nutritional regulation of the gene encoding the catalytic subunit of the rat apolipoprotein B mRNA editing enzyme: functional role in the modulation of apoB mRNA editing. J Lipid Res 36:414–428

    PubMed  Google Scholar 

  • Furukawa S, Sakata N, Ginsberg HN, Dixon JL (1992) Studies of the sites of intracellular degradation of apolipoprotein B in Hep G2 cells. J Biol Chem 267:22630–22638

    PubMed  Google Scholar 

  • Giannoni F, Bonen DK, Funahashi T, Hadjiagapiou C, Burant CF, Davidson NO (1994) Complementation of apolipoprotein B mRNA editing by human liver accompanied by secretion of apolipoprotein B48. J Biol Chem 269:5932–5936

    PubMed  Google Scholar 

  • Gillian-Daniel DL, Bates PW, Tebon A, Attie AD (2002) Endoplasmic reticulum localization of the low density lipoprotein receptor mediates presecretory degradation of apolipoprotein B. Proc Natl Acad Sci USA 99:4337–4342

    Article  PubMed  Google Scholar 

  • Ginsberg HN (2000) Insulin resistance and cardiovascular disease. J Clin Invest 106:453–458

    PubMed  Google Scholar 

  • Glass CK, Witztum JL (2001) Atherosclerosis. the road ahead. Cell 104:503–516

    Article  PubMed  Google Scholar 

  • Greeve J, Altkemper I, Dieterich JH, Greten H, Windler E (1993) Apolipoprotein B mRNA editing in 12 different mammalian species: hepatic expression is reflected in low concentrations of apoB-containing plasma lipoproteins. J Lipid Res 34:1367–1383

    PubMed  Google Scholar 

  • Greeve J, Axelos D, Welker S, Schipper M, Greten H (1998) Distinct promoters induce APOBEC-1 expression in rat liver and intestine. Arterioscler Thromb Vasc Biol 18:1079–1092

    PubMed  Google Scholar 

  • Greeve J, Chowdhury JR, Chowdhury NR (1996a) Induction of hepatic apolipoprotein B mRNA editing for reducing serum cholesterol levels: a breakthrough or a disaster? Hepatology 24:964–966

    PubMed  Google Scholar 

  • Greeve J, Jona VK, Chowdhury NR, Horwitz MS, Chowdhury JR (1996b) Hepatic gene transfer of the catalytic subunit of the apolipoprotein B mRNA editing enzyme results in a reduction of plasma LDL levels in normal and watanabe heritable hyperlipidemic rabbits. J Lipid Res 37:2001–2017

    PubMed  Google Scholar 

  • Greeve J, Navaratnam N, Scott J (1991) Characterization of the apolipoprotein B mRNA editing enzyme: no similarity to the proposed mechanism of RNA editing in kinetoplastid protozoa. Nucl Acids Res 19:3569–3576

    PubMed  Google Scholar 

  • Greeve J, Philipsen A, Krause K, Klapper W, Heidorn K, Castle BE, Janda J, Marcu KB, Parwaresch R (2003) Expression of activation-induced cytidine deaminase in human B-cell non-Hodgkin lymphomas. Blood 101:3574–3580

    Article  PubMed  Google Scholar 

  • Gusarova V, Brodsky JL, Fisher EA (2003) Apolipoprotein B100 exit from the ER is COPII dependent and its lipidation to very low density lipoprotein occurs post-ER. J Biol Chem

    Google Scholar 

  • Gusarova V, Caplan AJ, Brodsky JL, Fisher EA (2001) Apoprotein B degradation is promoted by the molecular chaperones hsp90 and hsp70. J Biol Chem 276:24891–24900

    Article  PubMed  Google Scholar 

  • Hagan DL, Kienzle B, Jamil H, Hariharan N (1994) Transcriptional regulation of human and hamster microsomal triglyceride transfer protein genes. Cell type-specific expression and response to metabolic regulators. J Biol Chem 269:28737–28744

    PubMed  Google Scholar 

  • Hardman DA, Pullinger CR, Hamilton RL, Kane JP, Malloy MJ (1991) Molecular and metabolic basis for the metabolic disorder normotriglyceridemic abetalipoproteinemia. J Clin Invest 88:1722–1729

    PubMed  Google Scholar 

  • Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (2003a) DNA deamination mediates innate immunity to retroviral infection. Cell 113:803–809

    PubMed  Google Scholar 

  • Harris RS, Petersen-Mahrt SK, Neuberger MS (2002a) RNA editing enzyme APOBEC1 and some of its homologs can act as DNA mutators. Mol Cell 10:1247–1253

    Article  PubMed  Google Scholar 

  • Harris RS, Sale JE, Petersen-Mahrt SK, Neuberger MS (2002b) AID is essential for immunoglobulin V gene conversion in a cultured B cell line. Curr Biol 12:435–438

    PubMed  Google Scholar 

  • Harris RS, Sheehy AM, Craig HM, Malim MH, Neuberger MS (2003b) DNA deamination: not just a trigger for antibody diversification but also a mechanism for defense against retroviruses. Nat Immunol 4:641–643

    Article  PubMed  Google Scholar 

  • Harris WS (1989) Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. J Lipid Res 30:785–807

    PubMed  Google Scholar 

  • Hebbachi AM, Brown AM, Gibbons GF (1999) Suppression of cytosolic triacylglycerol recruitment for very low density lipoprotein assembly by inactivation of microsomal triglyceride transfer protein results in a delayed removal of apoB-48 and apoB-100 from microsomal and Golgi membranes of primary rat hepatocytes. J Lipid Res 40:1758–1768

    PubMed  Google Scholar 

  • Hegde RS, Lingappa VR (1996) Sequence-specific alteration of the ribosome-membrane junction exposes nascent secretory proteins to the cytosol. Cell 85:217–228

    Article  PubMed  Google Scholar 

  • Hersberger M, Innerarity TL (1998) Two efficiency elements flanking the editing site of cytidine 6666 in the apolipoprotein B mRNA support mooring-dependent editing. J Biol Chem 273:9435–9442

    Article  PubMed  Google Scholar 

  • Hersberger M, Patarroyo-White S, Arnold KS, Innerarity TL (1999) Phylogenetic analysis of the apolipoprotein B mRNA-editing region. Evidence for a secondary structure between the mooring sequence and the 3′ efficiency element. J Biol Chem 274:34590–34597

    Article  PubMed  Google Scholar 

  • Herz J, Willnow TE (1995) Lipoprotein and receptor interactions in vivo. Curr Opin Lipidol 6:97–103

    PubMed  Google Scholar 

  • Hirano K, Min J, Funahashi T, Davidson NO (1997) Cloning and characterization of the rat apobec-1 gene: a comparative analysis of gene structure and promoter usage in rat and mouse. J Lipid Res 38:1103–1119

    PubMed  Google Scholar 

  • Hirano K, Young SG, Farese RV, Jr., Ng J, Sande E, Warburton C, Powell-Braxton LM, Davidson NO (1996) Targeted disruption of the mouse apobec-1 gene abolishes apolipoprotein B mRNA editing and eliminates apolipoprotein B48. J Biol Chem 271:9887–9890

    Article  PubMed  Google Scholar 

  • Hodges PE, Navaratnam N, Greeve JC, Scott J (1991) Site-specific creation of uridine from cytidine in apolipoprotein B mRNA editing. Nucl Acids Res 19:1197–1201

    PubMed  Google Scholar 

  • Huff MW, Burnett JR (1997) 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors and hepatic apolipoprotein B secretion. Curr Opin Lipidol 8:138–145

    PubMed  Google Scholar 

  • Hussain MM, Bakillah A, Nayak N, Shelness GS (1998) Amino acids 430–570 in apolipoprotein B are critical for its binding to microsomal triglyceride transfer protein. J Biol Chem 273:25612–25615

    PubMed  Google Scholar 

  • Innerarity TL, Weisgraber KH, Arnold KS, Mahley RW, Krauss RM, Vega GL, Grundy SM (1987) Familial defective apolipoprotein B-100: low density lipoproteins with abnormal receptor binding. Proc Natl Acad Sci USA 84:6919–6923

    PubMed  Google Scholar 

  • Jamil H, Chu CH, Dickson JK, Jr., Chen Y, Yan M, Biller SA, Gregg RE, Wetterau JR, Gordon DA (1998) Evidence that microsomal triglyceride transfer protein is limiting in the production of apolipoprotein B-containing lipoproteins in hepatic cells. J Lipid Res 39:1448–1454

    PubMed  Google Scholar 

  • Jarmuz A, Chester A, Bayliss J, Gisbourne J, Dunham I, Scott J, Navaratnam N (2002) An anthropoid-specific locus of orphan C to U RNA-editing enzymes on chromosome 22. Genomics 79:285–296

    Article  PubMed  Google Scholar 

  • Johnson DF, Poksay KS, Innerarity TL (1993) The mechanism for apo-B mRNA editing is deamination. Biochem Biophys Res Commun 195:1204–1210

    Article  PubMed  Google Scholar 

  • Jones B, Jones EL, Bonney SA, Patel HN, Mensenkamp AR, Eichenbaum-Voline S, Rudling M, Myrdal U, Annesi G, Naik S, Meadows N, Quattrone A, Islam SA, Naoumova RP, Angelin B, Infante R, Levy E, Roy CC, Freemont PS, Scott J, Shoulders CC (2003) Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders. Nat Genet 34:29–31

    Article  PubMed  Google Scholar 

  • Kane JP (1983) Apolipoprotein B: structural and metabolic heterogeneity. Annu Rev Physiol 45:637–650

    PubMed  Google Scholar 

  • Kim E, Cham CM, Veniant MM, Ambroziak P, Young SG (1998) Dual mechanisms for the low plasma levels of truncated apolipoprotein B proteins in familial hypobetalipoproteinemia. Analysis of a new mouse model with a nonsense mutation in the Apob gene. J Clin Invest 101:1468–1477

    Google Scholar 

  • Knott TJ, Pease RJ, Powell LM, Wallis SC, Rall SC, Jr., Innerarity TL, Blackhart B, Taylor WH, Marcel Y, Milne R, et al. (1986) Complete protein sequence and identification of structural domains of human apolipoprotein B. Nature 323:734–738

    Article  PubMed  Google Scholar 

  • Kozarsky KF, Bonen DK, Giannoni F, Funahashi T, Wilson JM, Davidson NO (1996) Hepatic expression of the catalytic subunit of the apolipoprotein B mRNA editing enzyme (apobec-1) ameliorates hypercholesterolemia in LDL receptor-deficient rabbits. Hum Gene Ther 7:943–957

    PubMed  Google Scholar 

  • Kummrow E, Hussain MM, Pan M, Marsh JB, Fisher EA (2002) Myristic acid increases dense lipoprotein secretion by inhibiting apoB degradation and triglyceride recruitment. J Lipid Res 43:2155–2163

    Article  PubMed  Google Scholar 

  • Kuriyama H, Yamashita S, Shimomura I, Funahashi T, Ishigami M, Aragane K, Miyaoka K, Nakamura T, Takemura K, Man Z, Toide K, Nakayama N, Fukuda Y, Lin MC, Wetterau JR, Matsuzawa Y (1998) Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation. Hepatology 27:557–562

    Article  PubMed  Google Scholar 

  • Kurowska EM, Spence JD, Jordan J, Wetmore S, Freeman DJ, Piche LA, Serratore P (2000) HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia. Am J Clin Nutr 72:1095–1100

    PubMed  Google Scholar 

  • Lau PP, Cahill DJ, Zhu HJ, Chan L (1995) Ethanol modulates apolipoprotein B mRNA editing in the rat. J Lipid Res 36:2069–2078

    PubMed  Google Scholar 

  • Lau PP, Xiong WJ, Zhu HJ, Chen SH, Chan L (1991) Apolipoprotein B mRNA editing is an intranuclear event that occurs posttranscriptionally coincident with splicing and polyadenylation. J Biol Chem 266:20550–20554

    PubMed  Google Scholar 

  • Lau PP, Zhu HJ, Baldini A, Charnsangavej C, Chan L (1994) Dimeric structure of a human apolipoprotein B mRNA editing protein and cloning and chromosomal localization of its gene. Proc Natl Acad Sci USA 91:8522–8526

    PubMed  Google Scholar 

  • Lee CH, Jeong TS, Choi YK, Hyun BH, Oh GT, Kim EH, Kim JR, Han JI, Bok SH (2001) Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem Biophys Res Commun 284:681–688

    PubMed  Google Scholar 

  • Lee CH, Olson P, Evans RM (2003a) Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology 144:2201–2207

    Article  PubMed  Google Scholar 

  • Lee MK, Moon SS, Lee SE, Bok SH, Jeong TS, Park YB, Choi MS (2003b) Naringenin 7-O-cetyl ether as inhibitor of HMG-CoA reductase and modulator of plasma and hepatic lipids in high cholesterol-fed rats. Bioorg Med Chem 11:393–398

    Article  PubMed  Google Scholar 

  • Leighton JK, Joyner J, Zamarripa J, Deines M, Davis RA (1990) Fasting decreases apolipoprotein B mRNA editing and the secretion of small molecular weight apoB by rat hepatocytes: evidence that the total amount of apoB secreted is regulated post-transcriptionally. J Lipid Res 31:1663–1668

    PubMed  Google Scholar 

  • Lellek H, Kirsten R, Diehl I, Apostel F, Buck F, Greeve J (2000) Purification and molecular cloning of a novel essential component of the apolipoprotein B mRNA editing enzyme-complex. J Biol Chem 275:19848–19856

    Article  PubMed  Google Scholar 

  • Lellek H, Welker S, Diehl I, Kirsten R, Greeve J (2002) Reconstitution of mRNA editing in yeast using a Gal4-apoB-Gal80 fusion transcript as the selectable marker. J Biol Chem 277:23638–23644

    PubMed  Google Scholar 

  • Leung GK, Veniant MM, Kim SK, Zlot CH, Raabe M, Bjorkegren J, Neese RA, Hellerstein MK, Young SG (2000) A deficiency of microsomal triglyceride transfer protein reduces apolipoprotein B secretion. J Biol Chem 275:7515–7520

    Article  PubMed  Google Scholar 

  • Levine GN, Keaney JF, Jr., Vita JA (1995) Cholesterol reduction in cardiovascular disease. Clinical benefits and possible mechanisms. N Engl J Med 332:512–521

    Article  PubMed  Google Scholar 

  • Levy-Wilson B, Paulweber B, Antes TJ, Goodart SA, Lee SY (2000) An open chromatin structure in a liver-specific enhancer that confers high level expression to human apolipoprotein b transgenes in mice. Mol Cell Biol Res Commun 4:206–211

    Article  PubMed  Google Scholar 

  • Levy-Wilson B, Paulweber B, Nagy BP, Ludwig EH, Brooks AR (1992) Nuclease-hypersensitive sites define a region with enhancer activity in the third intron of the human apolipoprotein B gene. J Biol Chem 267:18735–18743

    PubMed  Google Scholar 

  • Liang J, Ginsberg HN (2001) Microsomal triglyceride transfer protein binding and lipid transfer activities are independent of each other, but both are required for secretion of apolipoprotein B lipoproteins from liver cells. J Biol Chem 276:28606–28612

    Article  PubMed  Google Scholar 

  • Liang J, Wu X, Jiang H, Zhou M, Yang H, Angkeow P, Huang LS, Sturley SL, Ginsberg H (1998) Translocation efficiency, susceptibility to proteasomal degradation, and lipid responsiveness of apolipoprotein B are determined by the presence of beta sheet domains. J Biol Chem 273:35216–35221

    Article  PubMed  Google Scholar 

  • Liang JS, Kim T, Fang S, Yamaguchi J, Weissman AM, Fisher EA, Ginsberg HN (2003) Overexpression of the tumor autocrine motility factor receptor Gp78, a ubiquitin protein ligase, results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in HepG2 cells. J Biol Chem 278:23984–23988

    Article  PubMed  Google Scholar 

  • Liang S, Wu X, Fisher EA, Ginsberg HN (2000) The amino-terminal domain of apolipoprotein B does not undergo retrograde translocation from the endoplasmic reticulum to the cytosol. Proteasomal degradation of nascent apolipoprotein B begins at the carboxyl terminus of the protein, while apolipoprotein B is still in its original translocon. J Biol Chem 275:32003–32010

    Article  PubMed  Google Scholar 

  • Liao S, Lin J, Do H, Johnson AE (1997) Both lumenal and cytosolic gating of the aqueous ER translocon pore are regulated from inside the ribosome during membrane protein integration. Cell 90:31–41

    Article  PubMed  Google Scholar 

  • Liao W, Chang BH, Mancini M, Chan L (2003a) Ubiquitin-dependent and-independent proteasomal degradation of apoB associated with endoplasmic reticulum and Golgi apparatus, respectively, in HepG2 cells. J Cell Biochem 89:1019–1029

    Article  PubMed  Google Scholar 

  • Liao W, Hong SH, Chan BH, Rudolph FB, Clark SC, Chan L (1999a) APOBEC-2, a cardiac-and skeletal muscle-specific member of the cytidine deaminase supergene family. Biochem Biophys Res Commun 260:398–404

    Article  PubMed  Google Scholar 

  • Liao W, Hui TY, Young SG, Davis RA (2003b) Blocking microsomal triglyceride transfer protein interferes with apoB secretion without causing retention or stress in the ER. J Lipid Res 44:978–985

    Article  PubMed  Google Scholar 

  • Liao W, Kobayashi K, Chan L (1999b) Adenovirus-mediated overexpression of microsomal triglyceride transfer protein (MTP): mechanistic studies on the role of MTP in apolipoprotein B-100 biogenesis. Biochemistry 38:10215

    Article  PubMed  Google Scholar 

  • Liao W, Yeung SC, Chan L (1998) Proteasome-mediated degradation of apolipoprotein B targets both nascent peptides cotranslationally before translocation and full-length apolipoprotein B after translocation into the endoplasmic reticulum. J Biol Chem 273:27225–27230

    Article  PubMed  Google Scholar 

  • Lieu HD, Withycombe SK, Walker Q, Rong JX, Walzem RL, Wong JS, Hamilton RL, Fisher EA, Young SG (2003) Eliminating atherogenesis in mice by switching off hepatic lipoprotein secretion. Circulation 107:1315–1321

    Article  PubMed  Google Scholar 

  • Lin MC, Arbeeny C, Bergquist K, Kienzle B, Gordon DA, Wetterau JR (1994) Cloning and regulation of hamster microsomal triglyceride transfer protein. The regulation is independent from that of other hepatic and intestinal proteins which participate in the transport of fatty acids and triglycerides. J Biol Chem 269:29138–29145

    PubMed  Google Scholar 

  • Lin MC, Gordon D, Wetterau JR (1995) Microsomal triglyceride transfer protein (MTP) regulation in HepG2 cells: insulin negatively regulates MTP gene expression. J Lipid Res 36:1073–1081

    PubMed  Google Scholar 

  • Linden D, Lindberg K, Oscarsson J, Claesson C, Asp L, Li L, Gustafsson M, Boren J, Olofsson SO (2002) Influence of peroxisome proliferator-activated receptor alpha agonists on the intracellular turnover and secretion of apolipoprotein (Apo) B-100 and ApoB-48. J Biol Chem 277:23044–23053

    Article  PubMed  Google Scholar 

  • Linden D, Sjoberg A, Asp L, Carlsson L, Oscarsson J (2000) Direct effects of growth hormone on production and secretion of apolipoprotein B from rat hepatocytes. Am J Physiol Endocrinol Metab 279: E1335–E1346

    PubMed  Google Scholar 

  • Linnik KM, Herscovitz H (1998) Multiple molecular chaperones interact with apolipoprotein B during its maturation. The network of endoplasmic reticulum-resident chaperones (ERp72, GRP94, calreticulin, and BiP) interacts with apolipoprotein b regardless of its lipidation state. J Biol Chem 273:21368–21373

    Article  PubMed  Google Scholar 

  • Linton MF, Farese RV, Jr., Young SG (1993) Familial hypobetalipoproteinemia. J Lipid Res 34:521–541

    PubMed  Google Scholar 

  • Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424:99–103

    Article  PubMed  Google Scholar 

  • Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S (2003) Report of the National Heart, Lung, and Blood Institute Workshop on Lipoprotein(a) and Cardiovascular Disease: Recent Advances and Future Directions. Clin Chem 49:1785–1796

    PubMed  Google Scholar 

  • Mariani R, Chen D, Schrofelbauer B, Navarro F, Konig R, Bollman B, Munk C, Nymark-McMahon H, Landau NR (2003) Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell 114:21–31

    Article  PubMed  Google Scholar 

  • Marin M, Rose KM, Kozak SL, Kabat D (2003) HIV-1 Vif protein binds the editing enzyme APOBEC3G and induces its degradation. Nat Med

    Google Scholar 

  • McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM (1987) cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 330:132–137

    Article  PubMed  Google Scholar 

  • Mehta A, Driscoll DM (2002) Identification of domains in apobec-1 complementation factor required for RNA binding and apolipoprotein-B mRNA editing. RNA 8:69–82

    Article  PubMed  Google Scholar 

  • Mehta A, Kinter MT, Sherman NE, Driscoll DM (2000) Molecular cloning of apobec-1 complementation factor, a novel RNA-binding protein involved in the editing of apolipoprotein B mRNA. Mol Cell Biol 20:1846–1854

    Article  PubMed  Google Scholar 

  • Millar JS, Maugeais C, Fuki IV, Rader DJ (2002) Normal production rate of apolipoprotein B in LDL receptor-deficient mice. Arterioscler Thromb Vasc Biol 22:989–994

    Article  PubMed  Google Scholar 

  • Mitchell DM, Zhou M, Pariyarath R, Wang H, Aitchison JD, Ginsberg HN, Fisher EA (1998) Apoprotein B100 has a prolonged interaction with the translocon during which its lipidation and translocation change from dependence on the microsomal triglyceride transfer protein to independence. Proc Natl Acad Sci USA 95:14733–14738

    Article  PubMed  Google Scholar 

  • Monforte MT, Trovato A, Kirjavainen S, Forestieri AM, Galati EM, Lo Curto RB (1995) Biological effects of hesperidin, a Citrus flavonoid. (note II): hypolipidemic activity on experimental hypercholesterolemia in rat. Farmaco 50:595–599

    PubMed  Google Scholar 

  • Morrison JR, Paszty C, Stevens ME, Hughes SD, Forte T, Scott J, Rubin EM (1996) Apolipoprotein B RNA editing enzyme-deficient mice are viable despite alterations in lipoprotein metabolism. Proc Natl Acad Sci USA 93:7154–7159

    Article  PubMed  Google Scholar 

  • Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T (2000) Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell 102:553–563

    Article  PubMed  Google Scholar 

  • Muramatsu M, Sankaranand VS, Anant S, Sugai M, Kinoshita K, Davidson NO, Honjo T (1999) Specific expression of activation-induced cytidine deaminase (AID), a novel member of the RNA-editing deaminase family in germinal center B cells. J Biol Chem 274:18470–18476

    Article  PubMed  Google Scholar 

  • Nakamuta M, Chang BH, Hoogeveen R, Li WH, Chan L (1996a) Mouse microsomal triglyceride transfer protein large subunit: cDNA cloning, tissue-specific expression and chromosomal localization. Genomics 33:313–316

    Article  PubMed  Google Scholar 

  • Nakamuta M, Chang BH, Zsigmond E, Kobayashi K, Lei H, Ishida BY, Oka K, Li E, Chan L (1996b) Complete phenotypic characterization of apobec-1 knockout mice with a wildtype genetic background and a human apolipoprotein B transgenic background, and restoration of apolipoprotein B mRNA editing by somatic gene transfer of Apobec-1. J Biol Chem 271:25981–25988

    Article  PubMed  Google Scholar 

  • Nakamuta M, Oka K, Krushkal J, Kobayashi K, Yamamoto M, Li WH, Chan L (1995) Alternative mRNA splicing and differential promoter utilization determine tissue-specific expression of the apolipoprotein B mRNA-editing protein (Apobec1) gene inmice. Structure and evolution of Apobec1 and related nucleoside/nucleotide deaminases. J Biol Chem 270:13042–13056

    Article  PubMed  Google Scholar 

  • Navaratnam N, Bhattacharya S, Fujino T, Patel D, Jarmuz AL, Scott J (1995) Evolutionary origins of apoB mRNA editing: catalysis by a cytidine deaminase that has acquired a novel RNA-binding motif at its active site. Cell 81:187–195

    Article  PubMed  Google Scholar 

  • Navaratnam N, Fujino T, Bayliss J, Jarmuz A, How A, Richardson N, Somasekaram A, Bhattacharya S, Carter C, Scott J (1998) Escherichia coli cytidine deaminase provides a molecular model for ApoB RNA editing and a mechanism for RNA substrate recognition. J Mol Biol 275:695–714

    Article  PubMed  Google Scholar 

  • Navaratnam N, Morrison JR, Bhattacharya S, Patel D, Funahashi T, Giannoni F, Teng BB, Davidson NO, Scott J (1993) The p27 catalytic subunit of the apolipoprotein B mRNA editing enzyme is a cytidine deaminase. J Biol Chem 268:20709–20712

    PubMed  Google Scholar 

  • Okazaki I, Yoshikawa K, Kinoshita K, Muramatsu M, Nagaoka H, Honjo T (2003a) Activation-induced cytidine deaminase links class switch recombination and somatic hypermutation. Ann NY Acad Sci 987:1–8

    PubMed  Google Scholar 

  • Okazaki IM, Hiai H, Kakazu N, Yamada S, Muramatsu M, Kinoshita K, Honjo T (2003b) Constitutive expression of AID leads to tumorigenesis. J Exp Med 197:1173–1181

    Article  PubMed  Google Scholar 

  • Olofsson SO, Asp L, Boren J (1999) The assembly and secretion of apolipoprotein B-containing lipoproteins. Curr Opin Lipidol 10:341–346

    Article  PubMed  Google Scholar 

  • Packard CJ, Third JL, Shepherd J, Lorimer AR, Morgan HG, Lawrie TD (1976) Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients. Metabolism 25:995–1006

    Article  PubMed  Google Scholar 

  • Pan M, Liang J, Fisher EA, Ginsberg HN (2000) Inhibition of translocation of nascent apolipoprotein B across the endoplasmic reticulum membrane is associated with selective inhibition of the synthesis of apolipoprotein B. J Biol Chem 275:27399–27405

    PubMed  Google Scholar 

  • Pan M, Liang Js JS, Fisher EA, Ginsberg HN (2002) The late addition of core lipids to nascent apolipoprotein B100, resulting in the assembly and secretion of triglyceride-rich lipoproteins, is independent of both microsomal triglyceride transfer protein activity and new triglyceride synthesis. J Biol Chem 277:4413–4421

    Article  PubMed  Google Scholar 

  • Parhofer KG, Barrett PH, Bier DM, Schonfeld G (1992) Lipoproteins containing the truncated apolipoprotein, ApoB-89, are cleared from human plasma more rapidly than ApoB-100-containing lipoproteins in vivo. J Clin Invest 89:1931–1937

    PubMed  Google Scholar 

  • Parhofer KG, Daugherty A, Kinoshita M, Schonfeld G (1990) Enhanced clearance from plasma of low density lipoproteins containing a truncated apolipoprotein, apoB-89. J Lipid Res 31:2001–2007

    PubMed  Google Scholar 

  • Pariyarath R, Wang H, Aitchison JD, Ginsberg HN, Welch WJ, Johnson AE, Fisher EA (2001) Co-translational interactions of apoprotein B with the ribosome and translocon during lipoprotein assembly or targeting to the proteasome. J Biol Chem 276:541–550

    Article  PubMed  Google Scholar 

  • Patel SB, Grundy SM (1996) Interactions between microsomal triglyceride transfer protein and apolipoprotein B within the endoplasmic reticulum in a heterologous expression system. J Biol Chem 271:18686–18694

    Article  PubMed  Google Scholar 

  • Patterson AP, Chen Z, Rubin DC, Moucadel V, Iovanna JL, Brewer HB, Jr., Eggerman TL (2003) Developmental regulation of apolipoprotein B mRNA editing is an autonomous function of small intestine involving homeobox gene Cdx1. J Biol Chem 278:7600–7606

    Article  PubMed  Google Scholar 

  • Patterson AP, Tennyson GE, Hoeg JM, Sviridov DD, Brewer HB, Jr. (1992) Ontogenetic regulation of apolipoprotein B mRNA editing during human and rat development in vivo. Arterioscler Thromb 12:468–473

    PubMed  Google Scholar 

  • Pease RJ, Harrison GB, Scott J (1991) Cotranslocational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum. Nature 353:448–450

    Article  PubMed  Google Scholar 

  • Petersen-Mahrt SK, Harris RS, Neuberger MS (2002) AID mutates E. coli suggesting a DNA deamination mechanism for antibody diversification. Nature 418:99–103

    Article  PubMed  Google Scholar 

  • Petersen-Mahrt SK, Neuberger MS (2003) In vitro deamination of cytosine to uracil in single-stranded DNA by apolipoprotein B editing complex catalytic subunit 1 (APOBEC1). J Biol Chem 278:19583–19586

    Article  PubMed  Google Scholar 

  • Pham P, Bransteitter R, Petruska J, Goodman MF (2003) Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature 424:103–107

    Article  PubMed  Google Scholar 

  • Phung TL, Roncone A, Jensen KL, Sparks CE, Sparks JD (1997) Phosphoinositide 3-kinase activity is necessary for insulin-dependent inhibition of apolipoprotein B secretion by rat hepatocytes and localizes to the endoplasmic reticulum. J Biol Chem 272:30693–30702

    Article  PubMed  Google Scholar 

  • Powell LM, Wallis SC, Pease RJ, Edwards YH, Knott TJ, Scott J (1987) A novel form of tissue-specific RNA processing produces apolipoprotein-B48 in intestine. Cell 50:831–840

    Article  PubMed  Google Scholar 

  • Powell-Braxton L, Veniant M, Latvala RD, Hirano KI, Won WB, Ross J, Dybdal N, Zlot CH, Young SG, Davidson NO (1998) A mouse model of human familial hypercholesterolemia: markedly elevated low density lipoprotein cholesterol levels and severe atherosclerosis on a low-fat chow diet. Nat Med 4:934–938

    Article  PubMed  Google Scholar 

  • Pullinger CR, North JD, Teng BB, Rifici VA, Ronhild de Brito AE, Scott J (1989) The apolipoprotein B gene is constitutively expressed in HepG2 cells: regulation of secretion by oleic acid, albumin, and insulin, and measurement of the mRNA half-life. J Lipid Res 30:1065–1077

    PubMed  Google Scholar 

  • Qian X, Balestra ME, Innerarity TL (1997) Two distinct TATA-less promoters direct tissue-specific expression of the rat apo-B editing catalytic polypeptide 1 gene. J Biol Chem 272:18060–18070

    Article  PubMed  Google Scholar 

  • Qian X, Balestra ME, Yamanaka S, Boren J, Lee I, Innerarity TL (1998) Low expression of the apolipoprotein B mRNA-editing transgene in mice reduces LDL levels but does not cause liver dysplasia or tumors. Arterioscler Thromb Vasc Biol 18:1013–1020

    PubMed  Google Scholar 

  • Raabe M, Flynn LM, Zlot CH, Wong JS, Veniant MM, Hamilton RL, Young SG (1998) Knockout of the abetalipoproteinemia gene in mice: reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes. Proc Natl Acad Sci USA 95:8686–8691

    Article  PubMed  Google Scholar 

  • Raabe M, Veniant MM, Sullivan MA, Zlot CH, Bjorkegren J, Nielsen LB, Wong JS, Hamilton RL, Young SG (1999) Analysis of the role of microsomal triglyceride transfer protein in the liver of tissue-specific knockout mice. J Clin Invest 103:1287–1298

    PubMed  Google Scholar 

  • Rada C, Williams GT, Nilsen H, Barnes DE, Lindahl T, Neuberger MS (2002) Immunoglobulin isotype switching is inhibited and somatic hypermutation perturbed in UNG-deficient mice. Curr Biol 12:1748–1755

    Article  PubMed  Google Scholar 

  • Revy P, Muto T, Levy Y, Geissmann F, Plebani A, Sanal O, Catalan N, Forveille M, Dufourcq-Labelouse R, Gennery A, Tezcan I, Ersoy F, Kayserili H, Ugazio AG, Brousse N, Muramatsu M, Notarangelo LD, Kinoshita K, Honjo T, Fischer A, Durandy A (2000) Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell 102:565–575

    Article  PubMed  Google Scholar 

  • Richardson N, Navaratnam N, Scott J (1998) Secondary structure for the apolipoprotein B mRNA editing site. Au-binding proteins interact with a stem loop. J Biol Chem 273:31707–31717

    Article  PubMed  Google Scholar 

  • Rustaeus S, Lindberg K, Boren J, Olofsson SO (1995) Brefeldin A reversibly inhibits the assembly of apoB containing lipoproteins in McA-RH7777 cells. J Biol Chem 270:28879–28886

    Article  PubMed  Google Scholar 

  • Rustaeus S, Stillemark P, Lindberg K, Gordon D, Olofsson SO (1998) The microsomal triglyceride transfer protein catalyzes the post-translational assembly of apolipoprotein B-100 very low density lipoprotein in McA-RH7777 cells. J Biol Chem 273:5196–5203

    Article  PubMed  Google Scholar 

  • Schekman R, Orci L (1996) Coat proteins and vesicle budding. Science 271:1526–1533

    PubMed  Google Scholar 

  • Schonfeld G (2003) Familial hypobetalipoproteinemia: a review. J Lipid Res 44:878–883

    Article  PubMed  Google Scholar 

  • Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, Auwerx J (1996) PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBOJ 15:5336–5348

    Google Scholar 

  • Seishima M, Bisgaier CL, Davies SL, Glickman RM (1991) Regulation of hepatic apolipoprotein synthesis in the 17 alpha-ethinyl estradiol-treated rat. J Lipid Res 32:941–951

    PubMed  Google Scholar 

  • Shah RR, Knott TJ, Legros JE, Navaratnam N, Greeve JC, Scott J (1991) Sequence requirements for the editing of apolipoprotein B mRNA. J Biol Chem 266:16301–16304

    PubMed  Google Scholar 

  • Sharp D, Blinderman L, Combs KA, Kienzle B, Ricci B, Wager-Smith K, Gil CM, Turck CW, Bouma ME, Rader DJ, et al. (1993) Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinaemia. Nature 365:65–69

    Article  PubMed  Google Scholar 

  • Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418:646–650

    Article  PubMed  Google Scholar 

  • Sheehy AM, Gaddis NC, Malim MH (2003) The antiretroviral enzyme APOBEC3G is degraded by the proteasome in response to HIV-1 Vif. Nat Med

    Google Scholar 

  • Shin YW, Bok SH, Jeong TS, Bae KH, Jeoung NH, Choi MS, Lee SH, Park YB (1999) Hypocholesterolemic effect of naringin associated with hepatic cholesterol regulating enzyme changes in rats. Int J Vitam Nutr Res 69: 341–347

    PubMed  Google Scholar 

  • Shiomi M, Ito T (2001) MTP inhibitor decreases plasma cholesterol levels in LDL receptor-deficient WHHL rabbits by lowering the VLDL secretion. Eur J Pharmacol 431:127–131

    Article  PubMed  Google Scholar 

  • Singh RP, Dhawan P, Golden C, Kapoor GS, Mehta KD (1999) One-way cross-talk between p38(MAPK) and p42/44(MAPK). Inhibition of p38(MAPK) induces low density lipoprotein receptor expression through activation of the p42/44(MAPK) cascade. J Biol Chem 274:19593–19600

    Article  PubMed  Google Scholar 

  • Sjoberg A, Oscarsson J, Bostrom K, Innerarity TL, Eden S, Olofsson SO (1992) Effects of growth hormone on apolipoprotein-B (apoB) messenger ribonucleic acid editing, and apoB 48 and apoB 100 synthesis and secretion in the rat liver. Endocrinology 130:3356–3364

    Article  PubMed  Google Scholar 

  • Skalen K, Gustafsson M, Rydberg EK, Hulten LM, Wiklund O, Innerarity TL, Boren J (2002) Subendothelial retention of atherogenic lipoproteins in early atherosclerosis. Nature 417:750–754

    Article  PubMed  Google Scholar 

  • Soutar AK, Myant NB, Thompson GR (1977) Simultaneous measurement of apolipoprotein B turnover in very-low-and low-density lipoproteins in familial hypercholesterolaemia. Atherosclerosis 28:247–256

    Article  PubMed  Google Scholar 

  • Sparks JD, Phung TL, Bolognino M, Sparks CE (1996) Insulin-mediated inhibition of apolipoprotein B secretion requires an intracellular trafficking event and phosphatidylinositol 3-kinase activation: studies with brefeldin A and wortmannin in primary cultures of rat hepatocytes. Biochem J 313: 567–574

    PubMed  Google Scholar 

  • Sparks JD, Sparks CE (1990) Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes. J Biol Chem 265:8854–8862

    PubMed  Google Scholar 

  • Stillemark P, Boren J, Andersson M, Larsson T, Rustaeus S, Karlsson KA, Olofsson SO (2000) The assembly and secretion of apolipoprotein B-48-containing very low density lipoproteins in McA-RH7777 cells. J Biol Chem 275:10506–10513

    Article  PubMed  Google Scholar 

  • Stopak K, de Noronha C, Yonemoto W, Greene WC (2003) HIV-1 Vif blocks the antiviral activity of APOBEC3G by impairing both its translation and intracellular stability. Mol Cell 12:591–601

    Article  PubMed  Google Scholar 

  • Stumvoll M (2003) Thiazolidinediones-some recent developments. Expert Opin Investig Drugs 12:1179–1187

    PubMed  Google Scholar 

  • Taghibiglou C, Carpentier A, Van Iderstine SC, Chen B, Rudy D, Aiton A, Lewis GF, Adeli K (2000) Mechanisms of hepatic very low density lipoprotein overproduction in insulin resistance. Evidence for enhanced lipoprotein assembly, reduced intracellular ApoB degradation, and increased microsomal triglyceride transfer protein in a fructose-fed hamster model. J Biol Chem 275:8416–8425

    Article  PubMed  Google Scholar 

  • Taghibiglou C, Rashid-Kolvear F, Van Iderstine SC, Le-Tien H, Fantus IG, Lewis GF, Adeli K (2002) Hepatic very low density lipoprotein-ApoB overproduction is associated with attenuated hepatic insulin signaling and overexpression of protein-tyrosine phosphatase 1B in a fructose-fed hamster model of insulin resistance. J Biol Chem 277:793–803

    Article  PubMed  Google Scholar 

  • Takai Y, Sasaki T, Matozaki T (2001) Small GTP-binding proteins. Physiol Rev 81:153–208

    PubMed  Google Scholar 

  • Taskinen MR, Kuusi T, Helve E, Nikkila EA, Yki-Jarvinen H (1988) Insulin therapy induces antiatherogenic changes of serum lipoproteins in noninsulin-dependent diabetes. Arteriosclerosis 8:168–177

    PubMed  Google Scholar 

  • Teng B, Black DD, Davidson NO (1990) Apolipoprotein B messenger RNA editing is developmentally regulated in pig small intestine: nucleotide comparison of apolipoprotein B editing regions in five species. Biochem Biophys Res Commun 173:74–80

    Article  PubMed  Google Scholar 

  • Teng B, Burant CF, Davidson NO (1993) Molecular cloning of an apolipoprotein B messenger RNA editing protein. Science 260:1816–1819

    PubMed  Google Scholar 

  • Thorngate FE, Raghow R, Wilcox HG, Werner CS, Heimberg M, Elam MB (1994) Insulin promotes the biosynthesis and secretion of apolipoprotein B-48 by altering apolipoprotein B mRNA editing. Proc Natl Acad Sci USA 91:5392–5396

    PubMed  Google Scholar 

  • Tietge UJ, Bakillah A, Maugeais C, Tsukamoto K, Hussain M, Rader DJ (1999) Hepatic overexpression of microsomal triglyceride transfer protein (MTP) results in increased in vivo secretion of VLDL triglycerides and apolipoprotein B. J Lipid Res 40:2134–2139

    PubMed  Google Scholar 

  • Tran K, Thorne-Tjomsland G, DeLong CJ, Cui Z, Shan J, Burton L, Jamieson JC, Yao Z (2002) Intracellular assembly of very low density lipoproteins containing apolipoprotein B100 in rat hepatoma McA-RH7777 cells. J Biol Chem 277:31187–31200

    Article  PubMed  Google Scholar 

  • Tran K, Wang Y, DeLong CJ, Cui Z, Yao Z (2000) The assembly of very low density lipoproteins in rat hepatoma McA-RH7777 cells is inhibited by phospholipase A2 antagonists. J Biol Chem 275:25023–25030

    Article  PubMed  Google Scholar 

  • Twisk J, Gillian-Daniel DL, Tebon A, Wang L, Barrett PH, Attie AD (2000) The role of the LDL receptor in apolipoprotein B secretion. J Clin Invest 105:521–532

    PubMed  Google Scholar 

  • Verma R, Chen S, Feldman R, Schieltz D, Yates J, Dohmen J, Deshaies RJ (2000) Proteasomal proteomics: identification of nucleotide-sensitive proteasome-interacting proteins by mass spectrometric analysis of affinity-purified proteasomes. Mol Biol Cell 11:3425–3439

    PubMed  Google Scholar 

  • von Schacky C, Angerer P, Kothny W, Theisen K, Mudra H (1999) The effect of dietary omega-3 fatty acids on coronary atherosclerosis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 130:554–562

    PubMed  Google Scholar 

  • Vukmirica J, Tran K, Liang X, Shan J, Yuan J, Miskie BA, Hegele RA, Resh MD, Yao Z (2003) Assembly and secretion of very low density lipoproteins containing apolipoprotein B48 in transfected McA-RH7777 cells. Lack of evidence that palmitoylation of apolipoprotein B48 is required for lipoprotein secretion. J Biol Chem 278:14153–14161

    Article  PubMed  Google Scholar 

  • Wang CN, Hobman TC, Brindley DN (1995) Degradation of apolipoprotein B in cultured rat hepatocytes occurs in a post-endoplasmic reticulum compartment. J Biol Chem 270:24924–24931

    Article  PubMed  Google Scholar 

  • Wang H, Chen X, Fisher EA (1993) N-3 fatty acids stimulate intracellular degradation of apoprotein B in rat hepatocytes. J Clin Invest 91:1380–1389

    PubMed  Google Scholar 

  • Wang H, Yao Z, Fisher EA (1994) The effects of n-3 fatty acids on the secretion of carboxyl-terminally truncated forms of human apoprotein B. J Biol Chem 269:18514–18520

    PubMed  Google Scholar 

  • Wang S, McLeod RS, Gordon DA, Yao Z (1996) 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. J Biol Chem 271:14124–14133

    Article  PubMed  Google Scholar 

  • Wang SL, Du EZ, Martin TD, Davis RA (1997a) Coordinate regulation of lipogenesis, the assembly and secretion of apolipoprotein B-containing lipoproteins by sterol response element binding protein 1. J Biol Chem 272:19351–19358

    Article  PubMed  Google Scholar 

  • Wang Y, McLeod RS, Yao Z (1997b) 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. J Biol Chem 272:12272–12278

    Article  PubMed  Google Scholar 

  • Wang Y, Tran K, Yao Z (1999) The activity of microsomal triglyceride transfer protein is essential for accumulation of triglyceride within microsomes in McA-RH7777 cells. A unified model for the assembly of very low density lipoproteins. J Biol Chem 274:27793–27800

    Article  PubMed  Google Scholar 

  • Welty FK, Lichtenstein AH, Barrett PH, Dolnikowski GG, Ordovas JM, Schaefer EJ (1997) Decreased production and increased catabolism of apolipoprotein B-100 in apolipoprotein B-67/B-100 heterozygotes. Arterioscler Thromb Vasc Biol 17:881–888

    PubMed  Google Scholar 

  • Wetterau JR, Combs KA, Spinner SN, Joiner BJ (1990) Protein disulfide isomerase is a component of the microsomal triglyceride transfer protein complex. J Biol Chem265:9801–9807

    PubMed  Google Scholar 

  • Wetterau JR, Lin MC, Jamil H (1997) Microsomal triglyceride transfer protein. Biochim Biophys Acta 1345:136–150

    PubMed  Google Scholar 

  • Wilcox LJ, Borradaile NM, de Dreu LE, Huff MW (2001) Secretion of hepatocyte apoB is inhibited by the flavonoids, naringenin and hesperetin, via reduced activity and expression of ACAT2 and MTP. J Lipid Res 42:725–734

    PubMed  Google Scholar 

  • Wilson PW, Culleton BF (1998) Epidemiology of cardiovascular disease in the United States. Am J Kidney Dis 32: S56–S65

    PubMed  Google Scholar 

  • Windler EE, Greeve J, Daerr WH, Greten H (1988) Binding of rat chylomicrons and their remnants to the hepatic low-density-lipoprotein receptor and its role in remnant removal. Biochem J 252:553–561

    PubMed  Google Scholar 

  • Wu X, Sakata N, Lele KM, Zhou M, Jiang H, Ginsberg HN (1997) A two-site model for ApoB degradation in HepG2 cells. J Biol Chem 272:11575–11580

    Article  PubMed  Google Scholar 

  • Wu X, Zhou M, Huang LS, Wetterau J, Ginsberg HN (1996) Demonstration of a physical interaction between microsomal triglyceride transfer protein and apolipoprotein B during the assembly of ApoB-containing lipoproteins. J Biol Chem 271:10277–10281

    Article  PubMed  Google Scholar 

  • Yamanaka S, Balestra ME, Ferrell LD, Fan J, Arnold KS, Taylor S, Taylor JM, Innerarity TL (1995) Apolipoprotein B mRNA-editing protein induces hepatocellular carcinoma and dysplasia in transgenic animals. Proc Natl Acad Sci USA 92:8483–8487

    PubMed  Google Scholar 

  • Yamanaka S, Poksay KS, Arnold KS, Innerarity TL (1997) A novel translational repressor mRNA is edited extensively in livers containing tumors caused by the transgene expression of the apoB mRNA-editing enzyme. Genes Dev 11:321–333

    PubMed  Google Scholar 

  • Yamanaka S, Poksay KS, Balestra ME, Zeng GQ, Innerarity TL (1994) Cloning and mutagenesis of the rabbit ApoB mRNA editing protein. A zinc motif is essential for catalytic activity, and noncatalytic auxiliary factor(s) of the editing complex are widely distributed. J Biol Chem 269:21725–21734

    PubMed  Google Scholar 

  • Yang Y, Ballatori N, Smith HC (2002) Apolipoprotein B mRNA editing and the reduction in synthesis and secretion of the atherogenic risk factor, apolipoprotein B100 can be effectively targeted through TAT-mediated protein transduction. Mol Pharmacol 61:269–276

    Article  PubMed  Google Scholar 

  • Yeung SJ, Chen SH, Chan L (1996) Ubiquitin-proteasome pathway mediates intracellular degradation of apolipoprotein B. Biochemistry 35:13843–13848

    Article  PubMed  Google Scholar 

  • Young SG (1990) Recent progress in understanding apolipoprotein B. Circulation 82:1574–1594

    PubMed  Google Scholar 

  • Young SG, Krul ES, McCormick S, Farese RV, Jr., Linton MF (1996) Identification and characterization of truncated forms of apolipoprotein B in hypobetalipoproteinemia. Methods Enzymol 263:120–145

    PubMed  Google Scholar 

  • Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L (2003) The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424:94–98

    Article  PubMed  Google Scholar 

  • Zhou M, Fisher EA, Ginsberg HN (1998) Regulated Co-translational ubiquitination of apolipoprotein B100. A new paradigm for proteasomal degradation of a secretory protein. J Biol Chem 273:24649–24653

    Article  PubMed  Google Scholar 

  • Zhou M, Wu X, Huang LS, Ginsberg HN (1995) Apoprotein B100, an inefficiently translocated secretory protein, is bound to the cytosolic chaperone, heat shock protein 70. J Biol Chem 270:25220–25224

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Klinik für Allgemeine Innere Medizin, Inselspital-Universitätsspital Bern, 3010, Bern, Switzerland

    J. Greeve

Authors
  1. J. Greeve
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institute of Clinical Chemistry, University Hospital of Zurich, Rämistrasse 100, 8091, Zürich, Switzerland

    Arnold von Eckardstein

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Greeve, J. (2005). Inhibition of the Synthesis of Apolipoprotein B-Containing Lipoproteins. In: von Eckardstein, A. (eds) Atherosclerosis: Diet and Drugs. Handbook of Experimental Pharmacology, vol 170. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27661-0_18

Download citation

Publish with us

Policies and ethics

Search

Navigation