Journal of Lipid Research, Vol 34, 1209-1217, Copyright © 1993 by Lipid Research, Inc.

ARTICLES

Structural and functional changes in LDL after modification with both 4- hydroxynonenal and malondialdehyde

HF Hoff and J O'Neil
Department of Cell Biology, Cleveland Clinic Foundation, OH 44195.

Oxidized LDL is characterized by adduct formation between apolipoprotein (apo)B-100 in the low density lipoprotein (LDL) particles and reactive aldehydes such as 4-hydroxynonenal (HNE) and malondialdehyde (MDA), which are decomposition products of lipid peroxidation. Since LDL isolated from human atherosclerotic lesions was also shown to have interacted with HNE and MDA and to have undergone oxidation, we initiated a study to structurally and functionally characterize LDL modification with both HNE and MDA and to compare these characteristics with those of LDL modified individually with HNE and MDA. Using concentrations of LDL and HNE that alone resulted in extensive particle aggregation, modification at pH 7.4 with HNE plus MDA at 20 mM and above, resulted in the prevention of particle aggregation and less aggregation of apoB-100. Increases in electrophoretic mobility and blockage of exposed lysine residues on apoB were approximately additive for LDL modified at pH 7.4 with 6 mM HNE and MDA up to 20 mM compared to LDL modified individually with HNE or individually with MDA. When 125I-labeled LDL modified at pH 7.4 with HNE and increasing amounts of MDA was incubated with J774 macrophages, the doubly modified LDL showed a linear increase in degradation and in ACAT stimulation. LDL modified with MDA alone showed first a reduction in degradation and ACAT stimulation, due to reduced recognition by the LDL receptor. This was followed by an increase in degradation when further modification with MDA was performed at pH 6.4, but no or little increase in degradation when performed at pH 7.4.(ABSTRACT TRUNCATED AT 250 WORDS)
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. C. Kuiper, C. L. Miranda, J. D. Sowell, and J. F. Stevens Mercapturic Acid Conjugates of 4-Hydroxy-2-nonenal and 4-Oxo-2-nonenal Metabolites Are in Vivo Markers of Oxidative Stress J. Biol. Chem., June 20, 2008; 283(25): 17131 - 17138. [Abstract] [Full Text] [PDF]

				E. W. Trotter, E. J. Collinson, I. W. Dawes, and C. M. Grant Old Yellow Enzymes Protect against Acrolein Toxicity in the Yeast Saccharomyces cerevisiae. Appl. Envir. Microbiol., July 1, 2006; 72(7): 4885 - 4892. [Abstract] [Full Text] [PDF]

				M. J. Duryee, T. L. Freeman, M. S. Willis, C. D. Hunter, B. C. Hamilton III, H. Suzuki, D. J. Tuma, L. W. Klassen, and G. M. Thiele Scavenger Receptors on Sinusoidal Liver Endothelial Cells Are Involved in the Uptake of Aldehyde-Modified Proteins Mol. Pharmacol., November 1, 2005; 68(5): 1423 - 1430. [Abstract] [Full Text] [PDF]

				J. Sowell, B. Frei, and J. F. Stevens Vitamin C conjugates of genotoxic lipid peroxidation products: Structural characterization and detection in human plasma PNAS, December 28, 2004; 101(52): 17964 - 17969. [Abstract] [Full Text] [PDF]

				M. F. Khalil, W. D. Wagner, and I. J. Goldberg Molecular Interactions Leading to Lipoprotein Retention and the Initiation of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2004; 24(12): 2211 - 2218. [Abstract] [Full Text] [PDF]

				H. F. Hoff, J. O'Neil, Z. Wu, G. Hoppe, and R. L. Salomon Phospholipid Hydroxyalkenals: Biological and Chemical Properties of Specific Oxidized Lipids Present in Atherosclerotic Lesions Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 275 - 282. [Abstract] [Full Text] [PDF]

				S. Yamada, S. Kumazawa, T. Ishii, T. Nakayama, K. Itakura, N. Shibata, M. Kobayashi, K. Sakai, T. Osawa, and K. Uchida Immunochemical detection of a lipofuscin-like fluorophore derived from malondialdehyde and lysine J. Lipid Res., August 1, 2001; 42(8): 1187 - 1196. [Abstract] [Full Text] [PDF]

				I. Maor, T. Hayek, R. Coleman, and M. Aviram Plasma LDL Oxidation Leads to Its Aggregation in the Atherosclerotic Apolipoprotein E-Deficient Mice Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 2995 - 3005. [Abstract] [Full Text]

				B. Bjorkerud and S. Bjorkerud Contrary Effects of Lightly and Strongly Oxidized LDL With Potent Promotion of Growth Versus Apoptosis on Arterial Smooth Muscle Cells, Macrophages, and Fibroblasts Arterioscler. Thromb. Vasc. Biol., March 1, 1996; 16(3): 416 - 424. [Abstract] [Full Text]

				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]