Advertisement
JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M008885200 on April 2, 2001

J. Biol. Chem., Vol. 276, Issue 30, 27855-27863, July 27, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/30/27855    most recent
M008885200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fisher, E. A.
Right arrow Articles by Williams, K. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fisher, E. A.
Right arrow Articles by Williams, K. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

The Triple Threat to Nascent Apolipoprotein B
EVIDENCE FOR MULTIPLE, DISTINCT DEGRADATIVE PATHWAYS*

Edward A. FisherDagger §, Meihui PanDagger , Xiaoli ChenDagger , Xinye WuDagger , Hongxing WangDagger , Haris Jamil||, Janet D. Sparks**, and Kevin Jon WilliamsDagger Dagger §§

From the Dagger  Laboratory of Lipoprotein Research, The Zena and Michael A. Wiener Cardiovascular Institute and Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, the || Division of Metabolic Diseases, Bristol Myers Squibb Company, Princeton, New Jersey 08543, the ** Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, New York 14642, and the Dagger Dagger  Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes & Metabolic Diseases, Department of Medicine, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107

We previously showed that Omega -3 fatty acids reduce secretion of apolipoprotein B (apoB) from cultured hepatocytes by stimulating post-translational degradation. In this report, we now characterize this process, particularly in regard to the two known processes that degrade newly synthesized apoB, endoplasmic reticulum (ER)-associated degradation and re-uptake from the cell surface. First, we found that Omega -3-induced degradation preferentially reduces the secretion of large, assembled apoB-lipoprotein particles, and apoB polypeptide length is not a determinant. Second, based on several experimental approaches, ER-associated degradation is not involved. Third, re-uptake, the only process known to destroy fully assembled nascent lipoproteins, was clearly active in primary hepatocytes, but Omega -3-induced degradation of apoB continued even when re-uptake was blocked. Cell fractionation showed that Omega -3 fatty acids induced a striking loss of apoB100 from the Golgi, while sparing apoB100 in the ER, indicating a post-ER process. To determine the signaling involved, we used wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, which blocked most, if not all, of the Omega -3 fatty acid effect. Therefore, nascent apoB is subject to ER-associated degradation, re-uptake, and a third distinct degradative pathway that appears to target lipoproteins after considerable assembly and involves a post-ER compartment and PI3K signaling. Physiologic, pathophysiologic, and pharmacologic regulation of net apoB secretion may involve alterations in any of these three degradative steps.

* These studies were supported in part by National Institutes of Health Research Grants DK50376 (to J. D. S.), HL58541 and HL22263 (to E. A. F.), and HL58884 and HL38956 (to K. J. W.) and by the American Heart Association (Heritage Affiliate) (to E. A. F.). Portions of this work were presented at the 72nd Scientific Sessions of the American Heart Association, November, 1999 (1).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received salary support from National Institutes of Health Training Grant T32-HL07824.

§§ Received an Established Investigator Award from the American Heart Association. To whom correspondence may be addressed: Dept. of Medicine, Division of Endocrinology, Diabetes & Metabolic Diseases, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107. Tel.: 215-503-1272; Fax: 215-923-7932; E-mail: K_Williams@ac.jci.tju.edu.

§ To whom correspondence may be addressed: Box 1269, Mount Sinai School of Medicine, 1 Gustave Levy Place, New York, NY 10029. Tel.: 212-241-7152; Fax: 212-828-4178; E-mail: edward.fisher@mssm.edu.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
A. Grefhorst and E. J. Parks
Reduced insulin-mediated inhibition of VLDL secretion upon pharmacological activation of the liver X receptor in mice
J. Lipid Res., July 1, 2009; 50(7): 1374 - 1383.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
H. N. Ginsberg and E. A. Fisher
The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism
J. Lipid Res., April 1, 2009; 50(Supplement): S162 - S166.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
W. Martinet and G. R.Y. De Meyer
Autophagy in Atherosclerosis: A Cell Survival and Death Phenomenon With Therapeutic Potential
Circ. Res., February 13, 2009; 104(3): 304 - 317.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Manchekar, P. E. Richardson, Z. Sun, Y. Liu, J. P. Segrest, and N. Dashti
Charged Amino Acid Residues 997-1000 of Human Apolipoprotein B100 Are Critical for the Initiation of Lipoprotein Assembly and the Formation of a Stable Lipidated Primordial Particle in McA-RH7777 Cells
J. Biol. Chem., October 24, 2008; 283(43): 29251 - 29265.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
E. M. Allister, E. E. Mulvihill, P. H. R. Barrett, J. Y. Edwards, L. P. Carter, and M. W. Huff
Inhibition of apoB secretion from HepG2 cells by insulin is amplified by naringenin, independent of the insulin receptor
J. Lipid Res., October 1, 2008; 49(10): 2218 - 2229.
[Abstract] [Full Text] [PDF]

Home page
 Innate ImmunityHome page
N. Bartolome, B. Arteta, M. J. Martinez, Y. Chico, and B. Ochoa
Kupffer cell products and interleukin 1? directly promote VLDL secretion and apoB mRNA up-regulation in rodent hepatocytes
Innate Immunity, August 1, 2008; 14(4): 255 - 266.
[Abstract] [PDF]

Home page
 J. Cell Sci.Home page
Y. Ohsaki, J. Cheng, M. Suzuki, A. Fujita, and T. Fujimoto
Lipid droplets are arrested in the ER membrane by tight binding of lipidated apolipoprotein B-100
J. Cell Sci., July 15, 2008; 121(14): 2415 - 2422.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
M. Pan, V. Maitin, S. Parathath, U. Andreo, S. X. Lin, C. St. Germain, Z. Yao, F. R. Maxfield, K. J. Williams, and E. A. Fisher
Presecretory oxidation, aggregation, and autophagic destruction of apoprotein-B: A pathway for late-stage quality control
PNAS, April 15, 2008; 105(15): 5862 - 5867.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
P. Gastaminza, G. Cheng, S. Wieland, J. Zhong, W. Liao, and F. V. Chisari
Cellular Determinants of Hepatitis C Virus Assembly, Maturation, Degradation, and Secretion
J. Virol., March 1, 2008; 82(5): 2120 - 2129.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
V. Gusarova, J. Seo, M. L. Sullivan, S. C. Watkins, J. L. Brodsky, and E. A. Fisher
Golgi-associated Maturation of Very Low Density Lipoproteins Involves Conformational Changes in Apolipoprotein B, but Is Not Dependent on Apolipoprotein E
J. Biol. Chem., July 6, 2007; 282(27): 19453 - 19462.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
M. A. M. den Boer, P. J. Voshol, F. Kuipers, J. A. Romijn, and L. M. Havekes
Hepatic glucose production is more sensitive to insulin-mediated inhibition than hepatic VLDL-triglyceride production
Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1360 - E1364.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. J. Ng, N. Bourquard, V. Grijalva, S. Hama, D. M. Shih, M. Navab, A. M. Fogelman, A. J. Lusis, S. Young, and S. T. Reddy
Paraoxonase-2 Deficiency Aggravates Atherosclerosis in Mice Despite Lower Apolipoprotein-B-containing Lipoproteins: ANTI-ATHEROGENIC ROLE FOR PARAOXONASE-2
J. Biol. Chem., October 6, 2006; 281(40): 29491 - 29500.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
D. V. Chirieac, N. O. Davidson, C. E. Sparks, and J. D. Sparks
PI3-kinase activity modulates apo B available for hepatic VLDL production in apobec-1-/- mice
Am J Physiol Gastrointest Liver Physiol, September 1, 2006; 291(3): G382 - G388.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
W. Qiu, R. K. Avramoglu, A. C. Rutledge, J. Tsai, and K. Adeli
Mechanisms of glucosamine-induced suppression of the hepatic assembly and secretion of apolipoprotein B-100-containing lipoproteins
J. Lipid Res., August 1, 2006; 47(8): 1749 - 1761.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Biol. CellHome page
Y. Ohsaki, J. Cheng, A. Fujita, T. Tokumoto, and T. Fujimoto
Cytoplasmic Lipid Droplets Are Sites of Convergence of Proteasomal and Autophagic Degradation of Apolipoprotein B
Mol. Biol. Cell, June 1, 2006; 17(6): 2674 - 2683.
[Abstract] [Full Text] [PDF]

Home page
 J. Nutr.Home page
I. J. A. M. Jonkers, A. H. M. Smelt, H. M. G. Princen, F. Kuipers, J. A. Romijn, R. Boverhof, A. A. M. Masclee, and F. Stellaard
Fish Oil Increases Bile Acid Synthesis in Male Patients with Hypertriglyceridemia
J. Nutr., April 1, 2006; 136(4): 987 - 991.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
H. N. Ginsberg
REVIEW: Efficacy and Mechanisms of Action of Statins in the Treatment of Diabetic Dyslipidemia
J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 383 - 392.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
L. Li, P. Stillemark-Billton, C. Beck, P. Bostrom, L. Andersson, M. Rutberg, J. Ericsson, B. Magnusson, D. Marchesan, A. Ljungberg, et al.
Epigallocatechin gallate increases the formation of cytosolic lipid droplets and decreases the secretion of apoB-100 VLDL
J. Lipid Res., January 1, 2006; 47(1): 67 - 77.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
A. Grefhorst, J. Hoekstra, T. G. J. Derks, D. M. Ouwens, J. F. W. Baller, R. Havinga, L. M. Havekes, J. A. Romijn, and F. Kuipers
Acute hepatic steatosis in mice by blocking {beta}-oxidation does not reduce insulin sensitivity of very-low-density lipoprotein production
Am J Physiol Gastrointest Liver Physiol, September 1, 2005; 289(3): G592 - G598.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
X.-C. Jiang, Z. Li, R. Liu, X. P. Yang, M. Pan, L. Lagrost, E. A. Fisher, and K. J. Williams
Phospholipid Transfer Protein Deficiency Impairs Apolipoprotein-B Secretion from Hepatocytes by Stimulating a Proteolytic Pathway through a Relative Deficiency of Vitamin E and an Increase in Intracellular Oxidants
J. Biol. Chem., May 6, 2005; 280(18): 18336 - 18340.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. A. Sellers, L. Hou, D. R. Schoenberg, S. R. Batistuzzo de Medeiros, W. Wahli, and G. S. Shelness
Microsomal Triglyceride Transfer Protein Promotes the Secretion of Xenopus laevis Vitellogenin A1
J. Biol. Chem., April 8, 2005; 280(14): 13902 - 13905.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
K. J. Williams, M.-L. Liu, Y. Zhu, X. Xu, W. R. Davidson, P. McCue, and K. Sharma
Loss of Heparan N-Sulfotransferase in Diabetic Liver: Role of Angiotensin II
Diabetes, April 1, 2005; 54(4): 1116 - 1122.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
L. Asp, B. Magnusson, M. Rutberg, L. Li, J. Boren, and S.-O. Olofsson
Role of ADP Ribosylation Factor 1 in the Assembly and Secretion of ApoB-100-Containing Lipoproteins
Arterioscler. Thromb. Vasc. Biol., March 1, 2005; 25(3): 566 - 570.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
R. Vidal, S. Hernandez-Vallejo, T. Pauquai, O. Texier, M. Rousset, J. Chambaz, S. Demignot, and J.-M. Lacorte
Apple procyanidins decrease cholesterol esterification and lipoprotein secretion in Caco-2/TC7 enterocytes
J. Lipid Res., February 1, 2005; 46(2): 258 - 268.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
C. P. Oliva, L. Pisciotta, G. L. Volti, M. P. Sambataro, A. Cantafora, A. Bellocchio, A. Catapano, P. Tarugi, S. Bertolini, and S. Calandra
Inherited Apolipoprotein A-V Deficiency in Severe Hypertriglyceridemia
Arterioscler. Thromb. Vasc. Biol., February 1, 2005; 25(2): 411 - 417.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
D. V. Chirieac, H. L. Collins, J. Cianci, J. D. Sparks, and C. E. Sparks
Altered triglyceride-rich lipoprotein production in Zucker diabetic fatty rats
Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E42 - E49.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-L. Zhang, A. Hernandez-Ono, C. Ko, K. Yasunaga, L.-S. Huang, and H. N. Ginsberg
Regulation of Hepatic Apolipoprotein B-lipoprotein Assembly and Secretion by the Availability of Fatty Acids: I. DIFFERENTIAL RESPONSE TO THE DELIVERY OF FATTY ACIDS VIA ALBUMIN OR REMNANT-LIKE EMULSION PARTICLES
J. Biol. Chem., April 30, 2004; 279(18): 19362 - 19374.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
S. M. Post, M. Groenendijk, K. Solaas, P. C. N. Rensen, and H. M. G. Princen
Cholesterol 7{alpha}-Hydroxylase Deficiency in Mice on an APOE*3-Leiden Background Impairs Very-Low-Density Lipoprotein Production
Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 768 - 774.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
Z. Chen, R. L. Fitzgerald, G. Li, N. O. Davidson, and G. Schonfeld
Hepatic secretion of apoB-100 is impaired in hypobetalipoproteinemic mice with an apoB-38.9-specifying allele
J. Lipid Res., January 1, 2004; 45(1): 155 - 163.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
G. S. Shelness, L. Hou, A. S. Ledford, J. S. Parks, and R. B. Weinberg
Identification of the Lipoprotein Initiating Domain of Apolipoprotein B
J. Biol. Chem., November 7, 2003; 278(45): 44702 - 44707.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
C. Ko, S. M. O'Rourke, and L.-S. Huang
A fish oil diet produces different degrees of suppression of apoB and triglyceride secretion in human apoB transgenic mouse strains
J. Lipid Res., October 1, 2003; 44(10): 1946 - 1955.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Pawar and D. B. Jump
Unsaturated Fatty Acid Regulation of Peroxisome Proliferator-activated Receptor {alpha} Activity in Rat Primary Hepatoctes
J. Biol. Chem., September 19, 2003; 278(38): 35931 - 35939.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. Hevi and S. L. Chuck
Ferritins Can Regulate the Secretion of Apolipoprotein B
J. Biol. Chem., August 22, 2003; 278(34): 31924 - 31929.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. Zhang and H. Herscovitz
Nascent Lipidated Apolipoprotein B Is Transported to the Golgi as an Incompletely Folded Intermediate as Probed by Its Association with Network of Endoplasmic Reticulum Molecular Chaperones, GRP94, ERp72, BiP, Calreticulin, and Cyclophilin B
J. Biol. Chem., February 21, 2003; 278(9): 7459 - 7468.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
E. Kummrow, M. M. Hussain, M. Pan, J. B. Marsh, and E. A. Fisher
Myristic acid increases dense lipoprotein secretion by inhibiting apoB degradation and triglyceride recruitment
J. Lipid Res., December 1, 2002; 43(12): 2155 - 2163.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Singh, O. A. Batuman, H. O. Akman, M. H. Kedees, V. Vakil, and M. M. Hussain
Differential, Tissue-specific, Transcriptional Regulation of Apolipoprotein B Secretion by Transforming Growth Factor beta
J. Biol. Chem., October 11, 2002; 277(42): 39515 - 39524.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J. Vukmirica, T. Nishimaki-Mogami, K. Tran, J. Shan, R. S. McLeod, J. Yuan, and Z. Yao
The N-linked oligosaccharides at the amino terminus of human apoB are important for the assembly and secretion of VLDL
J. Lipid Res., September 1, 2002; 43(9): 1496 - 1507.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
N. M. Borradaile, L. E. de Dreu, P. H. R. Barrett, and M. W. Huff
Inhibition of hepatocyte apoB secretion by naringenin: enhanced rapid intracellular degradation independent of reduced microsomal cholesteryl esters
J. Lipid Res., September 1, 2002; 43(9): 1544 - 1554.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Kulinski, S. Rustaeus, and J. E. Vance
Microsomal Triacylglycerol Transfer Protein Is Required for Lumenal Accretion of Triacylglycerol Not Associated with ApoB, as Well as for ApoB Lipidation
J. Biol. Chem., August 23, 2002; 277(35): 31516 - 31525.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Linden, K. Lindberg, J. Oscarsson, C. Claesson, L. Asp, L. Li, M. Gustafsson, J. Boren, and S.-O. Olofsson
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., June 14, 2002; 277(25): 23044 - 23053.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. A. Rashid, S. Hevi, Y. Chen, F. Le Caherec, and S. L. Chuck
A Proteomic Approach Identifies Proteins in Hepatocytes That Bind Nascent Apolipoprotein B
J. Biol. Chem., June 7, 2002; 277(24): 22010 - 22017.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
J. S. Millar, C. Maugeais, I. V. Fuki, and D. J. Rader
Normal Production Rate of Apolipoprotein B in LDL Receptor-Deficient Mice
Arterioscler. Thromb. Vasc. Biol., June 1, 2002; 22(6): 989 - 994.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. A. Fisher and H. N. Ginsberg
Complexity in the Secretory Pathway: The Assembly and Secretion of Apolipoprotein B-containing Lipoproteins
J. Biol. Chem., May 10, 2002; 277(20): 17377 - 17380.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement