Intracellular degradation of newly synthesized apolipoprotein B

Journal of Lipid Research - Tập 38 - Trang 1937-1953 - 1997
Z Yao1, K Tran1, R S McLeod1
1Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ontario, Canada.

Tài liệu tham khảo

Borchardt, 1987, Intracellular assembly of very low density lipoproteins, J. Biol. Chem., 262, 16394, 10.1016/S0021-9258(18)49269-1 Ginsberg, 1995, Synthesis and secretion of apolipo-protein B from cultured liver cells, Curr. Opin. Lipidol., 6, 275, 10.1097/00041433-199510000-00006 Borén, 1992, The assembly and secretion of apoB-100-containing lipoproteins in HepG2 cells: apoB-100 is co-translationally integrated into lipoproteins, J. Biol. Chem., 267, 9858, 10.1016/S0021-9258(19)50173-9 Spring, 1992, Lipoprotein assembly: apoli-poprotein B size determines lipoprotein core circumference, J. Biol. Chem., 267, 14839, 10.1016/S0021-9258(18)42116-3 Rusiñol, 1993, Assembly of rat hepatic very low density lipoproteins in the endoplasmic reticulum, J. Biol. Chem., 268, 3555, 10.1016/S0021-9258(18)53730-3 Bamberger, 1990, Possible role of the Golgi apparatus in the assembly of very low density lipoproteins, Proc. Natl. Acad. Sci., USA., 87, 2390, 10.1073/pnas.87.7.2390 Cartwright, 1995, Intracellular events in the assembly of very low density lipoprotein lipids with apolipoprotein B in isolated rabbit hepatocytes, Biochem. J., 310, 897, 10.1042/bj3100897 Dixon, 1993, Regulation of hepatic secretion of apolipoprotein B-containing lipoproteins: information obtained from cultured liver cells, J. Lipid Res., 34, 167, 10.1016/S0022-2275(20)40744-8 Yao, 1994, Synthesis and secretion of hepatic apolipoprotein B-containing lipoproteins, Biochim. Biophys. Acta., 1212, 152, 10.1016/0005-2760(94)90249-6 Chan, 1992, Apolipoprotein B, the major protein component of triglyceride-rich and low density lipoproteins, J. Biol. Chem., 267, 25621, 10.1016/S0021-9258(18)35646-1 Davis, 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, 10.1016/S0021-9258(19)38770-8 Davis, 1989, Intrahepatic assembly of very low density lipoproteins: immunologic characterization of apolipoprotein B in lipoproteins and hepatic membrane fractions and its intracellular distribution, J. Lipid Res., 30, 1185, 10.1016/S0022-2275(20)38269-9 Dixon, 1992, Biosynthesis of lipoprotein: location of nascent apoA-I and apoB in the rough endoplasmic reticulum of chicken hepatocytes, J. Cell Biol., 117, 1161, 10.1083/jcb.117.6.1161 Wilkinson, 1993, Topography of apolipoprotein B in subcellular fractions of rabbit liver probed with a panel of monoclonal antibodies, J. Lipid Res., 34, 815, 10.1016/S0022-2275(20)39702-9 Zhou, 1995, Apoprotein B-100, an inefficiently translocated secretory protein, is bound to the cytosolic chaperone, heat shock protein 70, J. Biol. Chem., 270, 25220, 10.1074/jbc.270.42.25220 Wang, 1995, Degradation of apolipoprotein B in cultured rat hepatocytes occurs in a post-endoplasmic reticulum compartment, J. Biol. Chem., 270, 24924, 10.1074/jbc.270.42.24924 McLeod, 1996, Apolipoprotein B sequence requirements for hepatic very low density lipoprotein assembly: evidence that hydrophobic sequences within apolipoprotein B-48 mediate lipid recruitment, J. Biol. Chem., 271, 18445, 10.1074/jbc.271.31.18445 Macri, 1997, Studies on intracellular translocation of apolipoprotein B in a permeabilized HepG2 system, J. Biol. Chem., 272, 7328, 10.1074/jbc.272.11.7328 Yao, 1989, Head group specificity in the requirement of phosphatidylcholine biosynthesis for very low density lipoprotein secretion from cultured hepatocytes, J. Biol. Chem., 264, 11373, 10.1016/S0021-9258(18)60474-0 Rusiñol, 1993, Movement of apolipoprotein B into the lumen of microsomes from hepatocytes is disrupted in membranes enriched in phosphatidylmonomethylethanolamine, J. Biol. Chem., 268, 25168, 10.1016/S0021-9258(19)74584-0 Rusiñol, 1995, Inhibition of secretion of truncated apolipoprotein B by monomethylethanolamine is independent of the length of the apolipoprotein, J. Biol. Chem., 270, 13318, 10.1074/jbc.270.22.13318 Chen, 1986, The complete cDNA and ami no acid sequence of human apolipoprotein B-100, J. Biol. Chem., 261, 12918, 10.1016/S0021-9258(18)69248-8 Knott, 1986, Complete protein sequence and identification of structural domains of human apolipoprotein B., Nature., 323, 734, 10.1038/323734a0 Cladaras, 1986, The complete sequences and structural analysis of human apolipoprotein B-100: relationship between apoB-100 and apoB-48 forms, EMBO J., 5, 3495, 10.1002/j.1460-2075.1986.tb04675.x Law, 1986, Human liver apolipoprotein B-100 cDNA: complete nucleic acid and derived ami no acid sequence, Proc. Natl. Acad. Sci. USA., 83, 8142, 10.1073/pnas.83.21.8142 Paul, 1985, Folding patterns of porin and bacteriorhodopsin, EMBO J., 4, 1593, 10.1002/j.1460-2075.1985.tb03822.x Corsi, 1996, Mechanism of polypeptide translocation into the endoplasmic reticulum, J. Biol. Chem., 271, 30299, 10.1074/jbc.271.48.30299 Görlich, 1993, Protein translocation into proteoliposomes reconstituted from purified components of the endoplasmic reticulum membrane, Cell., 75, 615, 10.1016/0092-8674(93)90483-7 Chuck, 1991, New variation on the translocation of protein during early biogenesis of apolipoprotein B., Nature., 346, 382, 10.1038/346382a0 Pease, 1991, Cotranslo-cational insertion of apolipoprotein B into the inner leaflet of the endoplasmic reticulum, Nature., 353, 448, 10.1038/353448a0 Chuck, 1992, Pause transfer: a topogenic sequence in apolipoprotein B mediates stopping and restarting of translocation, Cell., 68, 9, 10.1016/0092-8674(92)90202-N Pease, 1995, Studies on the translocation of the ami no terminus of apolipoprotein B into the endoplasmic reticulum, J. Biol. Chem., 270, 7261, 10.1074/jbc.270.13.7261 Reithmeier, 1996, Assembly of proteins into membrane. In Biochemistry of Lipids, Lipoproteins and Membranes., 415 Hedge, 1996, Sequence-specific alteration of the ribosome-membrane junction exposes nascent secretory proteins to the cytosol, Cell., 85, 217, 10.1016/S0092-8674(00)81098-3 Gordon, 1995, Micro somal triglyceride transfer protein: a protein complex required for the assembly of lipoprotein particles, Trends, Cell Biol., 268, 22794 Farese, 1996, A novel function for apolipoprotein B: lipoprotein synthesis in the yolk sac is critical for maternal-fetal lipid transport in mice, J. Lipid Res., 37, 347, 10.1016/S0022-2275(20)37621-5 Thrift, 1992, Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in a nonhe-patic cell line, Proc. Natl. Acad. Sci. USA., 89, 9161, 10.1073/pnas.89.19.9161 Du, 1994, Proteolysis-coupled secretion of the N terminus of apolipoprotein B: characterization of a transient, translocation arrested intermediate, J. Biol. Chem., 269, 24169, 10.1016/S0021-9258(19)51064-X Adeli, 1994, Regulated intracellular degradation of apolipoprotein B in semipermeable HepG2 cells, J. Biol. Chem., 269, 9166, 10.1016/S0021-9258(17)37090-4 Sallach, 1995, Intracellular degradation of apolipoprotein B generates an N-terminal 70 kDa fragment in the endoplasmic reticulum, Biochim. Biophys. Acta., 1265, 29, 10.1016/0167-4889(95)00239-O Du, 1996, Translocation of apolipoprotein B across the endoplasmic reticulum is blocked in abetali-poproteinemia, J. Lipid Res., 37, 1309, 10.1016/S0022-2275(20)39160-4 Wetterau, 1992, Absence of microsomal triglyceride transfer protein in individuals with abetaii-poproteinemia, Science., 258, 999, 10.1126/science.1439810 Sharp, 1993, Cloning and gene defects in microsomal triglyceride transfer protein associated with abetalipoproteinemia, Nature., 365, 65, 10.1038/365065a0 Shoulders, 1993, Abetalipoproteinemia is caused by defects of the gene encoding the 97 kDa subunit of a microsomal triglyceride transfer protein, Hum. Mol. Genet., 12, 2109, 10.1093/hmg/2.12.2109 Gordon, 1994, 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, Proc. Natl. Acad. Sci. USA., 91, 7628, 10.1073/pnas.91.16.7628 Leiper, 1994, Microsomal triglyceride transfer protein, the abetalipoproteinemia gene product, mediates the secretion of apolipoprotein B-con-taining lipoproteins from heterologous cells, J. Biol. Chem., 269, 21951, 10.1016/S0021-9258(17)31740-4 Wang, 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, 10.1074/jbc.271.24.14124 Patel, 1996, Interactions be tween microsomal triglyceride transfer protein and apolipoprotein B within the endoplasmic reticulum in a heterologous expression system, J. Biol. Chem., 271, 18686, 10.1074/jbc.271.31.18686 Ingram, 1996, Apolipoprotein B-100 destined for lipoprotein assembly and intracellular degradation undergoes efficient translocation across the endoplasmic reticulum membrane, J. Lipid Res., 37, 2202, 10.1016/S0022-2275(20)37302-8 Leiper, 1996, Systematic expression of the complete coding sequence of apoB-100 does not reveal transmembrane determinants, J. Lipid Res., 37, 2215, 10.1016/S0022-2275(20)37303-X Brodsky, 1993, Reconstitution of protein translocation from solubilized yeast membranes reveals topologically distinct roles for BiP and cvtosolic Hsc 70, J. Cell Biol., 120, 95, 10.1083/jcb.120.1.95 McCracken, 1996, Assembly of ER-associated protein degradation in vitro: dependence of cytosol, calnexin, and ATP, J. Cell Biol., 132, 291, 10.1083/jcb.132.3.291 Shelness, 1994, Apolipoprotein B-48-membrane interactions: absence of transmembrane localization in nonhepatic: cells, J. Biol. Chem., 269, 9310, 10.1016/S0021-9258(17)37109-0 Sparks, 1992, Impaired hepatic apolipoprotein B and E translation in streptozotocin diabetic rats, J. Clin. Invest., 89, 1418, 10.1172/JCI115731 Sparks, 1990, Insulin modulation of hepatic synthesis and secretion of apolipoprotein B by rat hepatocytes, J. Biol. Chem., 265, 8854, 10.1016/S0021-9258(19)38966-5 Adeli, 1992, Insulin modulation of human apolipoprotein B mRNA translation: studies in an in vitro cell-free system from HepG2 cells, Biochem. Cell Biol., 70, 1301, 10.1139/o92-177 Bonnardel, 1995, In HepG2 cells, translocation, not degradation, determines the fate of the de novo synthesized apolipoprotein B., J. Biol. Chem., 270, 28892, 10.1074/jbc.270.48.28892 Farese, 1996, Phenotypic analysis of mice expressing exclusively apolipoprotein B-48 or apolipoprotein B-100, Proc. Natl. Acad. Sci. USA., 93, 6393, 10.1073/pnas.93.13.6393 Kane, 1980, Heterogeneity of apolipoprotein B. Isolation of a new species from human chylomicrons, Proc. Natl. Acad. Sci. USA., 77, 2465, 10.1073/pnas.77.5.2465 Elovson, 1981, Apolipoprotein B is structurally and metabolically heterogeneous in the rat, Proc. Natl. Acad. Sci. USA., 78, 157, 10.1073/pnas.78.1.157 Sparks, 1981, Metabolic heterogeneity of apolipoprotein B in the rat, J. lipid Res., 59, 693 Krishnaiah, 1980, Apolipoprotein B variant derived from rat intestine, Proc. Natl. Acad. Sci. USA., 77, 3806, 10.1073/pnas.77.7.3806 Rusiñol, 1997, In vitro reconstitution of assembly of apolipoprotein B-48-con-laining lipoproteins, J. Biol. Chem., 272, 8019, 10.1074/jbc.272.12.8019 Wang, 1996, Distinct translocation efficiency of apoB-100 and apoB- 48 may influence hepatic lipoprotein assembly, Circulation., 94, 1 Herscovitz, 1995, Murine mammary-derived cells secrete the N-terminal 41% of human apolipoprotein B on high density lipoprotein-sized lipoproteins containing a triacylglycerol rich core, Proc. Natl. Acad. Sci. USA., 92, 659, 10.1073/pnas.92.3.659 Yao, 1991, Expression of car-boxyl-terminally truncated forms of human apolipoprotein B in rat hepatoma cells: evidence that the length of apolipoprotein B has a major effect on the buoyant density of the secreted lipoproteins, J. Biol. Chem., 266, 3300, 10.1016/S0021-9258(18)49988-7 McLeod, 1994, Carboxyl-terminal truncation impairs lipid recruitment by apolipoprotein B-100 but does not affect secretion of the truncated apolipoprotein B-containing lipoproteins, J. Biol. Chem., 269, 2852, 10.1016/S0021-9258(17)42021-7 Yao, 1992, Elimination of apolipoprotein B-48 formation in rat hepatoma cell lines transfected with mutant human apolipoprotein B cDNA constructs, J. Biol. Chem., 267, 1175, 10.1016/S0021-9258(18)48411-6 Heinemann, 1994, Alternative polyadenylation of apolipoprotein B RNA is a major cause of B-48 protein formation in rat hepatoma cell lines transfected with human apoB-100 minigenes, J. Lipid Res., 35, 2200, 10.1016/S0022-2275(20)39926-0 Johnson, 1993, Human apolipoprotein B cryptic polyadenylation sites are activated in McA-RH7777 cells, Circulation., 88, 1 Benoist, 1997, Co-translational degradation of apolipoprotein B-100 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:, 10.1074/jbc.272.33.20435 Segrest, 1994, ApoB-100 has a penta-partite structure composed of three amphipathic α-heli-cal domains alternating with two amphipathic β-strand domains, Arterioscler. Thromb., 14, 1674, 10.1161/01.ATV.14.10.1674 Cartwright, 1993, Transit and sorting of apolipoprotein B within the endoplasmic reticulum and Golgi compartments of isolated hepatocytes from normal and orotic acid-fed rats, J. Biol. Chem., 268, 20937, 10.1016/S0021-9258(19)36877-2 Borén, 1993, Influence of triacylglycerol biosynthesis rate on the assembly of apoB-100-containing lipoproteins in HepG2 cells, Arterioscler. Thromb., 13, 1743, 10.1161/01.ATV.13.12.1743 Adeli, 1997, Intracellular assembly and degradation of apolipoprotein B-100-containing lipoproteins in digitonin-permeabilized HepG2 cells, J. Biol. Chem., 272, 5031, 10.1074/jbc.272.8.5031 Sato, 1990, Degradation of newly synthesized apolipoprotein B-100 in a pre-Golgi compartment, J. Biol. Chem., 265, 11880, 10.1016/S0021-9258(19)38481-9 Furukawa, 1992, Studies of the sites of intracellular degradation of apolipoprotein B in HepG2 cells, J. Biol. Chem., 267, 22630, 10.1016/S0021-9258(18)41719-X Yeung, 1996, Ubiquitin-proteasome pathway mediates intracellular degradation of apolipoprotein B., Biochemistry., 35, 13843, 10.1021/bi9618777 Goldberg, 1995, Functions of the proteasome: the lysis at the end of the tunnel, Science., 268, 522, 10.1126/science.7725095 Hilt, 1996, Proteasomes: destruction as a programme, Trends Biochem. Sci., 21, 96, 10.1016/S0968-0004(96)10012-8 Wiertz, 1996, Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction, Nature., 384, 432, 10.1038/384432a0 Teckman, 1996, The endoplasmic reticulum degradation pathway for mutant secretory proteins alpha-antitrypsin Z and S is distinct from that for an unassembled membrane protein, J. Biol. Chem., 271, 13215, 10.1074/jbc.271.22.13215 Qu, 1996, Degradation of a mutant secretory protein, al-anutrypsin Z, in the endoplasmic reticulum requires proteasome activity, J. Biol. Chem., 271, 22791, 10.1074/jbc.271.37.22791 Sakata, 1993, Proteolysis and lipid-facilitated translocation are distinct but competitive processes that regulate secretion of apolipoprotein B in HepG2 cells, J. Biol. Chem., 268, 22967, 10.1016/S0021-9258(19)49411-8 Hayes, 1996, Roles of molecular chaperones in protein degradation, J. Cell Biol., 132, 255, 10.1083/jcb.132.3.255 Zhou, 1996, Evidence that a rapidly turning over protein, normally degraded by proteasomes, regulates hsp72 gene transcription in HepG2 cells, J. Biol. Chem., 271, 24769, 10.1074/jbc.271.40.24769 Zhou, 1996, Increased level of the cytosolic chaperone, heat shock protein 70, are associated with increased degradation of nascent apoB in HepG2 cells, Circulation., 94, 1 van Remmen, 1996, Expression of genes coding for antioxidant enzymes and heat shock proteins is altered in primary cultures of rat hepatocytes, J. Cell. Physiol., 166, 453, 10.1002/(SICI)1097-4652(199602)166:2<453::AID-JCP24>3.0.CO;2-A Rechsteiner, 1996, PEST sequences and regulation by proteolysis, Trends Biochem. Sci., 21, 267, 10.1016/S0968-0004(96)10031-1 Sparks, 1993, Hormonal regulation of lipoprotein assembly and secretion, Curr. Opin. Lipidol., 44, 177, 10.1097/00041433-199306000-00002 Sparks, 1988, Secretion of high and low molecular weight phosphorylated apolipoprotein B by hepatocytes from control and diabetic rats, J. Biol. Chem., 263, 5001, 10.1016/S0021-9258(18)60665-9 Yang, 1989, Structure of apolipoprotein B-100 of human low density lipoproteins, Arteriosclerosis., 9, 96, 10.1161/01.ATV.9.1.96 Ou, 1993, Association of folding intermediates of glycoproteins with calnexin during protein maturation, Nature., 364, 771, 10.1038/364771a0 Hebert, 1995, Glucose trimming and reglucosylation determine glycoprotein association with calnexin in the endoplasmic reticulum, Cell., 81, 425, 10.1016/0092-8674(95)90395-X Siuta-Mangano, 1982, Association and assembly of triglyceride and phospholipid with glycosylated and unglycosylated apoproteins of very low density lipoprotein in the intact liver cell, J. Biol. Chem., 257, 11463, 10.1016/S0021-9258(18)33782-7 Wong, 1994, Differentiation of intra-hepatic membrane-bound and secretory apolipoprotein B by monoclonal antibodies: membrane-bound apolipoprotein B is more glycosylated, Biochemisliy., 33, 1923, 10.1021/bi00173a040 Herscovitz, 1991, Expression, secretion, and lipid-binding characterization of the N-terminal 17% of apolipoprotein B., Proc. Natl. Acad. Sci. USA., 88, 7313, 10.1073/pnas.88.16.7313 Huang, 1989, Hypobetalipoprotein-emia due to a apolipoprotein B gene exon 21 deletion derived by AIu-Alu recombination, J. Biol. Chem., 264, 11394, 10.1016/S0021-9258(18)60477-6 Talmud, 1994, Donor splice mutation generates a lipid-associated apolipoprotein B27.6 in a patient with homozygous hypobetalipoproteinemia, J. Lipid Res., 35, 468, 10.1016/S0022-2275(20)41197-6 Parhofer, 1996, Positive linear correlation between the length of truncated apolipoprotein B and its secretion rate: in vivo studies in human apoB-89, apoB-75, apoB-54.8, and apoB-31 heterozygotes, J. Lipid Res., 37, 844, 10.1016/S0022-2275(20)37582-9 Linton, 1993, Familial hypobetalipoproteinemia, J. Lipid Res., 34, 521, 10.1016/S0022-2275(20)39976-4 McLeod, 1994, Sequence determinants of intracellular degradation of newly synthesized apolipoprotein B., Circulation., 90, 1 Selby, 1995, Level of apolipoprotein B mRNA has an important effect on the synthesis and secretion of apolipoprotein B-containing lipoproteins: studies on transfected hepatoma cell lines expressing recombinant human apolipoprotein B., Arterioscler. Thromb. Vasc. Biol., 15, 1900, 10.1161/01.ATV.15.11.1900 Hussain, 1995, Characterization of recombinant human apoB-48-containing lipoproteins in rat hepatoma McA-RH7777 cells transfected with apoB-48 cDNA: over-expression of apoB-48 decreases synthesis of endogenous apoB-100, Arterioscler. Thromb. Vasc. Biol., 15, 485, 10.1161/01.ATV.15.4.485 Vermeulen, 1997, Phosphatidylcholine biosynthesis is required for secretion of truncated apolipoprotein Bs from McArdle RH7777 cells only when neutral lipid core is formed, J. Lipid Res., 38, 447, 10.1016/S0022-2275(20)37253-9 Otsu, 1994, Protein disulfide isomerase associates with misfolded human lysozyme in vivo, J. Biol. Chem., 269, 6874, 10.1016/S0021-9258(17)37456-2 Otsu, 1995, A possible role of ER-60 protease in the degradation of misfolded proteins in endoplasmic reticulum, J. Biol. Chem., 270, 14958, 10.1074/jbc.270.25.14958 Urade, 1993, Protein degradation by ERp72 from rat and mouse liver endoplasmic reticulum, J. Biol. Chem., 268, 22004, 10.1016/S0021-9258(20)80640-1 Adeli, 1996, Apolipoprotein B-100 is associated with an ER60-like protease in HepG2 cells: the role of ER60 in intracellular degradation of apolipoprotein B., Circulation., 94, 1 Wang, 1996, The isomerase activity of PDI is required for efficient apoB production from insect cells but is not required for tire MTP-facilitated apoB secretion, Circulation., 94, 1 Wu, 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, 10.1074/jbc.271.17.10277 Hiller, 1996, ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway, Science., 273, 1725, 10.1126/science.273.5282.1725 Werner, 1996, Proteasome-dependent endoplasmic reticulum-associated protein degradation: an unconventional route to a familiar fate, Proc. Natl. Acad. Sci. USA., 93, 13797, 10.1073/pnas.93.24.13797 McLeod, 1996, The requirement of microsomal triglyceride transfer protein in apoB lipoprotein secretion correlates with the lipid binding ability of apoB, Circulation., 94, 1 Sparks, 1994, Insulin regulation of triacylglycerol-rich lipoprotein synthesis and secretion, Biochim. Biophys. Acta., 1215, 9, 10.1016/0005-2760(94)90088-4 Verkade, 1993, Impaired biosynthesis of phosphatidylcholine causes a decrease in the number of very low density lipoprotein particles in the Golgi but not in the endoplasmic reticulum of rat liver, J. Biol. Chem., 268, 24990, 10.1016/S0021-9258(19)74561-X Wang, 1993, X-3 fatty acids stimulate intracellular degradation of apoprotein B irr rat hepatocytes, J. Clin. Invest., 91, 1380, 10.1172/JCI116340 Fast, 1995, Nascent VLDL phos-pholipid composition is altered when phosphatidylcholine biosynthesis is inhibited: evidence for a novel mechanism that regulates VLDL secretion, Biochim. Biophys. Acta., 1258, 159, 10.1016/0005-2760(95)00116-T Cartwright, 1996, Intracellular degradation in the regulation of secretion of apolipoprotein B-100 by rabbit hepatocytes, Biochem. J., 314, 977, 10.1042/bj3140977 Dixon, 1991, Oleate stimulates secretion of apolipoprotein B-containing lipoproteins from HepG2 cells by inhibiting early degradation of apolipoprotein B., J. Biol. Chem., 266, 5080, 10.1016/S0021-9258(19)67758-6 Sparks, 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, 10.1042/bj3130567 Ye, 1992, Human plasma lipoproteins regulate apolipoprotein E secretion from a post-Golgi compartment, J. Biol. Chem., 267, 21961, 10.1016/S0021-9258(19)36706-7 Ye, 1993, Inhibition of apolipoprotein E degradation in a post-Golgi compartment by a cysteine protease inhibitor, J. Biol. Chem., 268, 8497, 10.1016/S0021-9258(18)52902-1 Wang, 1994, The effect of n-3 fatty acids on the secretion of carboxy-truncated forms of human apoprotein B., J. Biol. Chem., 269, 18514, 10.1016/S0021-9258(17)32339-6 Fisher, 1995, Relationship between the two-step lipidation model for apoB and n-3 fatty acids, Circulation., 92, 1 Howell, 1982, Heterogeneity of lipoprotein particles in hepatic Golgi fractions, J. Cell Biol., 92, 833, 10.1083/jcb.92.3.833 Hamilton, 1991, Isolation and properties of nascent lipoproteins from highly purified rat hepatocytic Golgi fractions, J. Lipid Res., 32, 529, 10.1016/S0022-2275(20)42077-2 Yao, 1988, The active synthesis of phosphatidylcholine is required for very low density lipoprotein secretion from rat hepatocytes, J. Biol. Chem., 263, 2298, 10.1016/S0021-9258(18)69166-5 Fainaru, 1977, Evidence that a separate particle containing B-apolipoprotein is present in high-density lipoproteins from perfused rat liver, Metabolism., 26, 999, 10.1016/0026-0495(77)90017-8 Borén, 1994, Studies on the assembly of apolipoprotein B-100- and B-48-con-taining very low density lipoproteins in McA-RH7777 cells, J. Biol. Chem., 269, 25879, 10.1016/S0021-9258(18)47328-0 Innerarity, 1996, Biosynthesis of apolipoprotein B-48-con-taining lipoproteins: regulation by novel post-transcriptional mechanisms, J. Biol. Chem., 271, 2353, 10.1074/jbc.271.5.2353 Chen, 1993, Hepatic polysomes that contain apoprotein B mRNA have unusual physical properties, J. Biol. Chem., 268, 21007, 10.1016/S0021-9258(19)36886-3 Phung, 1996, Phos-phoinositide 3-kinase is necessary for insulin-induced apolipoprotein B degradation in rat hepatocytes, and localizes to a microsome fraction containing apolipoprotein B mRNA, Circulation., 94, 1 Wang, 1997, 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, 10.1074/jbc.272.19.12272 Nishimaki-Mogami, 1996, Biochim. Biophys. Acta., 1304, 21, 10.1016/S0005-2760(96)00100-2 Hamilton, 1986, Nascent high density lipoproteins from liver perfusates of orotic acid-fed rats, J. Lipid Res., 27, 967, 10.1016/S0022-2275(20)38772-1 Hay, 1988, Apolipoproteins of the orotic acid fatty liver: implications for the biogenesis of plasma lipoproteins, J. Lipid Res., 29, 981, 10.1016/S0022-2275(20)38473-X Wang, 1995, Effects of dexamethasone on the synthesis, degradation, and secretion of apolipoprotein B in cultured rat hepatocytes, Arterioscler. Thromb. Vasc. Biol., 15, 1481, 10.1161/01.ATV.15.9.1481 Rustaeus, 1995, Brefeldin A reversibly inhibits the assembly of apoB-containing lipoproteins in McA-RH7777 cells, J. Biol. Chem., 270, 28879, 10.1074/jbc.270.48.28879 Klausner, 1992, Brefeldin A: insights into the control of membrane traffic and organelle structure, J. Cell Biol., 116, 1071, 10.1083/jcb.116.5.1071 Rothman, 1994, Mechanisms of intracellular protein transport, Nature., 372, 55, 10.1038/372055a0 Gordon, 1996, 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, J. Biol. Chem., 271, 33047, 10.1074/jbc.271.51.33047 Czech, 1995, Molecular actions of insulin on glucose transport, Annu. Rev. Nutr., 15, 441, 10.1146/annurev.nu.15.070195.002301