HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fong, L. G. Articles by Steinberg, D. Search for Related Content PubMed PubMed Citation Articles by Fong, L. G. Articles by Steinberg, D. Social Bookmarking                      What's this?

Journal of Lipid Research, Vol 28, 1466-1477, Copyright © 1987 by Lipid Research, Inc.

ARTICLES

Nonenzymatic oxidative cleavage of peptide bonds in apoprotein B-100

LG Fong, S Parthasarathy, JL Witztum and D Steinberg
Department of Medicine, University of California, San Diego, La Jolla 92093.

Incubation of low density lipoprotein (LDL) with endothelial cells converts it to a form that is avidly degraded by macrophages via the acetyl LDL receptor. This modification has previously been shown to be accompanied by extensive breakdown of the major LDL protein (apoB-100) to smaller peptides. ApoB-100 is known to undergo partial degradation during isolation and purification which is commonly attributed to proteolytic enzymes derived from plasma or to contaminant bacteria. In the present studies addition of any of ten different inhibitors of proteolytic enzymes failed to inhibit the endothelial cell-induced degradation of LDL apoB-100 or its subsequent enhanced rate of degradation by macrophages (termed biological modification). Conversely, deliberate digestion of LDL with any of five well- characterized proteolytic enzymes degraded apoB-100 extensively but did not cause biological modification. The disappearance of intact apoB-100 during incubation with endothelial cells paralleled the formation of thiobarbituric acid (TBA)-reactive substances and the breakdown could be completely prevented by the addition of antioxidants or metal chelators. Finally, the incubation of LDL with a free radical- generating system (dihydroxyfumaric acid and Fe3+-ADP) in the absence of cells resulted in the breakdown of apoB-100. These results suggest that the breakdown of apoB-100 during oxidative modification of LDL, whether cell-induced or catalyzed by transition metals, is not mediated by proteolytic enzymes but rather is linked to oxidative attack on the polypeptide chain, either directly or secondary to peroxidation of closely associated LDL lipids.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				E Matsuura and L. Lopez Autoimmune-mediated atherothrombosis Lupus, October 1, 2008; 17(10): 879 - 888. [Abstract] [PDF]

				R. Carnevale, P. Pignatelli, L. Lenti, B. Buchetti, V. Sanguigni, S. Di Santo, and F. Violi LDL are oxidatively modified by platelets via GP91phox and accumulate in human monocytes FASEB J, March 1, 2007; 21(3): 927 - 934. [Abstract] [Full Text] [PDF]

				S. Uchiyama, T. Shimizu, and T. Shirasawa CuZn-SOD Deficiency Causes ApoB Degradation and Induces Hepatic Lipid Accumulation by Impaired Lipoprotein Secretion in Mice J. Biol. Chem., October 20, 2006; 281(42): 31713 - 31719. [Abstract] [Full Text] [PDF]

				L. Chancharme, P. Therond, F. Nigon, S. Zarev, A. Mallet, E. Bruckert, and M. J. Chapman LDL particle subclasses in hypercholesterolemia: molecular determinants of reduced lipid hydroperoxide stability J. Lipid Res., March 1, 2002; 43(3): 453 - 462. [Abstract] [Full Text] [PDF]

				C. Edelstein, K. Nakajima, D. Pfaffinger, and A. M. Scanu Oxidative events cause degradation of apoB-100 but not of apo[a] and facilitate enzymatic cleavage of both proteins J. Lipid Res., October 1, 2001; 42(10): 1664 - 1670. [Abstract] [Full Text] [PDF]

				A. Roland, R. A. Patterson, and D. S. Leake Measurement of Copper-Binding Sites on Low Density Lipoprotein Arterioscler. Thromb. Vasc. Biol., April 1, 2001; 21(4): 594 - 602. [Abstract] [Full Text] [PDF]

				J. M. Holopainen, O. P. Medina, A. J. Metso, and P. K. J. Kinnunen Sphingomyelinase Activity Associated with Human Plasma Low Density Lipoprotein. POSSIBLE FUNCTIONAL IMPLICATIONS J. Biol. Chem., May 26, 2000; 275(22): 16484 - 16489. [Abstract] [Full Text] [PDF]

				K. L. Gillotte, S. Hörkkö, J. L. Witztum, and D. Steinberg Oxidized phospholipids, linked to apolipoprotein B of oxidized LDL, are ligands for macrophage scavenger receptors J. Lipid Res., May 1, 2000; 41(5): 824 - 833. [Abstract] [Full Text]

				H. Kataoka, N. Kume, S. Miyamoto, M. Minami, T. Murase, T. Sawamura, T. Masaki, N. Hashimoto, and T. Kita Biosynthesis and Post-translational Processing of Lectin-like Oxidized Low Density Lipoprotein Receptor-1 (LOX-1). N-LINKED GLYCOSYLATION AFFECTS CELL-SURFACE EXPRESSION AND LIGAND BINDING J. Biol. Chem., February 25, 2000; 275(9): 6573 - 6579. [Abstract] [Full Text] [PDF]

				S. Parthasarathy, N. Santanam, S. Ramachandran, and O. Meilhac Oxidants and antioxidants in atherogenesis: an appraisal J. Lipid Res., December 1, 1999; 40(12): 2143 - 2157. [Abstract] [Full Text] [PDF]

				X. Xing, J. Baffic, and C. P. Sparrow LDL oxidation by activated monocytes: characterization of the oxidized LDL and requirement for transition metal ions J. Lipid Res., November 1, 1998; 39(11): 2201 - 2208. [Abstract] [Full Text]

				H. Moriwaki, N. Kume, T. Sawamura, T. Aoyama, H. Hoshikawa, H. Ochi, E. Nishi, T. Masaki, and T. Kita Ligand Specificity of LOX-1, a Novel Endothelial Receptor for Oxidized Low Density Lipoprotein Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1541 - 1547. [Abstract] [Full Text] [PDF]

				V. Terpstra, D. A. Bird, and D. Steinberg Evidence that the lipid moiety of oxidized low density lipoprotein plays a role in its interaction with macrophage receptors PNAS, February 17, 1998; 95(4): 1806 - 1811. [Abstract] [Full Text] [PDF]

				I. C. Gelissen, A. J. Brown, E. L. Mander, L. Kritharides, R. T. Dean, and W. Jessup Sterol Efflux Is Impaired from Macrophage Foam Cells Selectively Enriched with 7-Ketocholesterol J. Biol. Chem., July 26, 1996; 271(30): 17852 - 17860. [Abstract] [Full Text] [PDF]

				P. Lesnik, C. Dentan, A. Vonica, M. Moreau, and M. J. Chapman Tissue Factor Pathway Inhibitor Activity Associated With LDL Is Inactivated by Cell- and Copper-Mediated Oxidation Arterioscler. Thromb. Vasc. Biol., August 1, 1995; 15(8): 1121 - 1130. [Abstract] [Full Text]