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Science 6 November 1992:
Vol. 258. no. 5084, pp. 999 - 1001
DOI: 10.1126/science.1439810
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Articles

Science, Vol 258, Issue 5084, 999-1001
Copyright © 1992 by American Association for the Advancement of Science

articles

Absence of microsomal triglyceride transfer protein in individuals with abetalipoproteinemia

Wetterau JR, LP Aggerbeck, ME Bouma, C Eisenberg, A Munck, M Hermier, J Schmitz, G Gay, DJ Rader, and RE Gregg

Department of Metabolic Diseases, Bristol-Myers Squibb, Princeton, NJ 08543-4000.

Abetalipoproteinemia is a human genetic disease that is characterized by a defect in the assembly or secretion of plasma very low density lipoproteins and chylomicrons. The microsomal triglyceride transfer protein (MTP), which is located in the lumen of microsomes isolated from the liver and intestine, has been proposed to function in lipoprotein assembly. MTP activity and the 88-kilodalton component of MTP were present in intestinal biopsy samples from eight control individuals but were absent in four abetalipoproteinemic subjects. This finding suggests that a defect in MTP is the basis for abetalipoproteinemia and that MTP is indeed required for lipoprotein assembly.


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Niacin Accelerates Intracellular ApoB Degradation by Inhibiting Triacylglycerol Synthesis in Human Hepatoblastoma (HepG2) Cells.
F.-Y. Jin, V. S. Kamanna, and M. L. Kashyap (1999)
Arterioscler Thromb Vasc Biol 19, 1051-1059
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Liver-specific Inactivation of the Abetalipoproteinemia Gene Completely Abrogates Very Low Density Lipoprotein/Low Density Lipoprotein Production in a Viable Conditional Knockout Mouse.
B. H.-J. Chang, W. Liao, L. Li, M. Nakamuta, D. Mack, and L. Chan (1999)
J. Biol. Chem. 274, 6051-6055
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Prechylomicron transport vesicle: isolation and partial characterization.
N. S. Kumar and C. M. Mansbach II (1999)
Am J Physiol Gastrointest Liver Physiol 276, G378-G386
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Identification of Domains in Apolipoprotein B100 That Confer a High Requirement for the Microsomal Triglyceride Transfer Protein.
E. Nicodeme, F. Benoist, R. McLeod, Z. Yao, J. Scott, C. C. Shoulders, and T. Grand-Perret (1999)
J. Biol. Chem. 274, 1986-1993
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Translocation-arrested Apolipoprotein B Evades Proteasome Degradation via a Sterol-sensitive Block in Ubiquitin Conjugation.
E. Z. Du, J. F. Fleming, S.-L. Wang, G. M. Spitsen, and R. A. Davis (1999)
J. Biol. Chem. 274, 1856-1862
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Identification of two polymorphisms in the promoter of the microsomal triglyceride transfer protein (MTP) gene: lack of association with lipoprotein profiles.
S.-M. Herrmann, O. Poirier, V. Nicaud, A. Evans, J.-B. Ruidavets, G. Luc, D. Arveiler, C. Bao-Sheng, and F. Cambien (1998)
J. Lipid Res. 39, 2432-2435
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The HMG-CoA Reductase Inhibitor Atorvastatin Increases the Fractional Clearance Rate of Postprandial Triglyceride-Rich Lipoproteins in Miniature Pigs.
J. R. Burnett, P. H. R. Barrett, P. Vicini, D. B. Miller, D. E. Telford, S. J. Kleinstiver, and M. W. Huff (1998)
Arterioscler Thromb Vasc Biol 18, 1906-1914
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Regulated Co-translational Ubiquitination of Apolipoprotein B100. A NEW PARADIGM FOR PROTEASOMAL DEGRADATION OF A SECRETORY PROTEIN.
M. Zhou, E. A. Fisher, and H. N. Ginsberg (1998)
J. Biol. Chem. 273, 24649-24653
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Knockout of the abetalipoproteinemia gene in mice: Reduced lipoprotein secretion in heterozygotes and embryonic lethality in homozygotes.
M. Raabe, L. M. Flynn, C. H. Zlot, J. S. Wong, M. M. Veniant, R. L. Hamilton, and S. G. Young (1998)
PNAS 95, 8686-8691
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Evidence that microsomal triglyceride transfer protein is limiting in the production of apolipoprotein B-containing lipoproteins in hepatic cells.
H. Jamil, C.-H. Chu, J. K . Dickson , Jr., Y. Chen, M. Yan, S. A. Biller, R. E. Gregg, J. R. Wetterau, and D. A. Gordon (1998)
J. Lipid Res. 39, 1448-1454
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Regulation of microsomal triglyceride transfer protein mRNA expression by endotoxin and cytokines.
M. Navasa, D. A. Gordon, N. Hariharan, H. Jamil, J. K. Shigenaga, A. Moser, W. Fiers, A. Pollock, C. Grunfeld, and K. R. Feingold (1998)
J. Lipid Res. 39, 1220-1230
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13-Hydroxy octadecadienoic acid (13-HODE) inhibits triacylglycerol-rich lipoprotein secretion by CaCo-2 cells.
S. Murthy, E. Born, S. Mathur, and F. J. Field (1998)
J. Lipid Res. 39, 1254-1262
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A Common Functional Polymorphism in the Promoter Region of the Microsomal Triglyceride Transfer Protein Gene Influences Plasma LDL Levels.
F. Karpe, B. Lundahl, E. Ehrenborg, P. Eriksson, and A. Hamsten (1998)
Arterioscler Thromb Vasc Biol 18, 756-761
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Endocrinopathies in the Family of Endoplasmic Reticulum (ER) Storage Diseases: Disorders of Protein Trafficking and the Role of ER Molecular Chaperones.
P. S. Kim and P. Arvan (1998)
Endocr. Rev. 19, 173-202
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The Microsomal Triglyceride Transfer Protein Catalyzes the Post-translational Assembly of Apolipoprotein B-100 Very Low Density Lipoprotein in McA-RH7777 Cells.
S. Rustaeus, P. Stillemark, K. Lindberg, D. Gordon, and S.-O. Olofsson (1998)
J. Biol. Chem. 273, 5196-5203
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Participation of the microsomal triglyceride transfer protein in lipoprotein assembly in Caco-2 cells: interaction with saturated and unsaturated dietary fatty acids.
M. M. J. van Greevenbroek, M. G. Robertus-Teunissen, D. W. Erkelens, and T. W. A. de Bruin (1998)
J. Lipid Res. 39, 173-185
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Assembly and Secretion of VLDL in Nondifferentiated Caco-2 Cells Stably Transfected With Human Recombinant ApoB48 cDNA.
J. Luchoomun, Z. Zhou, A. Bakillah, H. Jamil, and M. M. Hussain (1997)
Arterioscler Thromb Vasc Biol 17, 2955-2963
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The Enzymatic and Non-enzymatic Roles of Protein-disulfide Isomerase in Apolipoprotein B Secretion.
L. Wang, D. G. Fast, and A. D. Attie (1997)
J. Biol. Chem. 272, 27644-27651
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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.
F. Benoist and T. Grand-Perret (1997)
J. Biol. Chem. 272, 20435-20442
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Metabolic Basis of Hypotriglyceridemic Effects of Insulin in Normal Men.
R. Malmstrom, C. J. Packard, T. D. G. Watson, S. Rannikko, M. Caslake, D. Bedford, P. Stewart, H. Yki-Jarvinen, J. Shepherd, and M.-R. Taskinen (1997)
Arterioscler Thromb Vasc Biol 17, 1454-1464
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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.
Y. Wang, R. S. McLeod, and Z. Yao (1997)
J. Biol. Chem. 272, 12272-12278
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