Journal of Lipid Research, Vol 35, 1570-1582, Copyright © 1994 by Lipid Research, Inc.

ARTICLES

Predominance of esterified hydroperoxy-linoleic acid in human monocyte- oxidized LDL

VA Folcik and MK Cathcart
Cleveland Clinic Foundation, OH 44194.

Low density lipoprotein that was oxidized by activated human monocytes was analyzed to determine the identity of oxidized fatty acids present and the conditions required for their formation. The oxidized lipids were also analyzed under conditions allowing preservation of their oxidation state. Using reversed-phase high performance liquid chromatography (HPLC) analysis of native and saponified lipid extracts of oxidized low density lipoprotein (LDL), we found that the major fatty acid oxidation product was esterified hydroperoxyoctadecadienoic acid (HPODE), the oxidized product of the most abundant polyunsaturated fatty acid in human LDL, linoleic acid. Although some esterified hydroxyoctadecadienoic acid (HODE) was also detected, the reduction of HPODE to HODE did not appear to be monocyte-dependent. Essentially all of the HPODE was found to be esterified with the majority being esterified to cholesterol followed by phospholipids and generally following the abundance of esterified linoleic acid within the lipid classes. The percent of cholesteryl linoleate converted to cholesteryl HPODE and cholesteryl HODE at the end of the 24-h incubation was determined to be approximately 13.5%. The formation of oxidized esterified linoleic acid in the LDL was shown to require immunological activation of the human monocytes, a previously observed requirement for general LDL oxidation in this culture system. The oxidized esterified linoleic acid was present in the supernatant with the LDL and was not cell-associated. HPODE formation on LDL was prevented by including superoxide dismutase (SOD) or eicosatetraynoic acid (ETYA) during the 24-h coincubation of activated monocytes with LDL whereas indomethacin was without effect. The analysis of the lipid oxidation products in oxidized LDL can provide insight into the mechanisms involved in oxidation of LDL by activated human monocytes.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Obinata, T. Hattori, S. Nakane, K. Tatei, and T. Izumi Identification of 9-Hydroxyoctadecadienoic Acid and Other Oxidized Free Fatty Acids as Ligands of the G Protein-coupled Receptor G2A J. Biol. Chem., December 9, 2005; 280(49): 40676 - 40683. [Abstract] [Full Text] [PDF]

				R. Natarajan, M. A. Reddy, K. U. Malik, S. Fatima, and B. V. Khan Signaling Mechanisms of Nuclear Factor-{kappa}B-Mediated Activation of Inflammatory Genes by 13-Hydroperoxyoctadecadienoic Acid in Cultured Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., September 1, 2001; 21(9): 1408 - 1413. [Abstract] [Full Text] [PDF]

				N. R. T. Damasceno, H. Goto, F. M. D. Rodrigues, C. T. S. Dias, F. S. Okawabata, D. S. P. Abdalla, and M. Gidlund Soy Protein Isolate Reduces the Oxidizability of LDL and the Generation of Oxidized LDL Autoantibodies in Rabbits with Diet-Induced Atherosclerosis J. Nutr., November 1, 2000; 130(11): 2641 - 2647. [Abstract] [Full Text] [PDF]

				E. A. Bey and M. K. Cathcart In vitro knockout of human p47phox blocks superoxide anion production and LDL oxidation by activated human monocytes J. Lipid Res., March 1, 2000; 41(3): 489 - 495. [Abstract] [Full Text]

				G. M. Chisolm III, S. L. Hazen, P. L. Fox, and M. K. Cathcart The Oxidation of Lipoproteins by Monocytes-Macrophages. BIOCHEMICAL AND BIOLOGICAL MECHANISMS J. Biol. Chem., September 10, 1999; 274(37): 25959 - 25962. [Full Text] [PDF]

				N. Santanam, N. Auge, M. Zhou, C. Keshava, and S. Parthasarathy Overexpression of Human Catalase Gene Decreases Oxidized Lipid-Induced Cytotoxicity in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., August 1, 1999; 19(8): 1912 - 1917. [Abstract] [Full Text] [PDF]

				N. Auge, N. Santanam, N. Mori, C. Keshava, and S. Parthasarathy Uptake of 13-Hydroperoxylinoleic Acid by Cultured Cells Arterioscler. Thromb. Vasc. Biol., April 1, 1999; 19(4): 925 - 931. [Abstract] [Full Text] [PDF]

				M. Van Heek, D. Schmitt, P. Toren, M. K. Cathcart, and P. E. DiCorleto Cholesteryl Hydroperoxyoctadecadienoate from Oxidized Low Density Lipoprotein Inactivates Platelet-derived Growth Factor J. Biol. Chem., July 31, 1998; 273(31): 19405 - 19410. [Abstract] [Full Text] [PDF]

				S. L. Bursten, D. Federighi, J. Wald, B. Meengs, W. Spickler, and E. Nudelman Lisofylline Causes Rapid and Prolonged Suppression of Serum Levels of Free Fatty Acids J. Pharmacol. Exp. Ther., January 1, 1998; 284(1): 337 - 345. [Abstract] [Full Text]

				D. M. Guidot, S. L. Bursten, G. C. Rice, R. B. Chaney, J. W. Singer, A. J. Repine, B. M. Hybertson, and J. E. Repine Modulating phosphatidic acid metabolism decreases oxidative injury in rat lungs Am J Physiol Lung Cell Mol Physiol, November 1, 1997; 273(5): L957 - L966. [Abstract] [Full Text] [PDF]

				V. A. Folcik, R. Aamir, and M. K. Cathcart Cytokine Modulation of LDL Oxidation by Activated Human Monocytes Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 1954 - 1961. [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]

				M. Camacho, N. Godessart, R. Antón, M. Garca, and L. Vila Interleukin-1 Enhances the Ability of Cultured Human Umbilical Vein Endothelial Cells to Oxidize Linoleic Acid J. Biol. Chem., July 21, 1995; 270(29): 17279 - 17286. [Abstract] [Full Text] [PDF]

				S. S. Davies, A. V. Pontsler, G. K. Marathe, K. A. Harrison, R. C. Murphy, J. C. Hinshaw, G. D. Prestwich, A. St. Hilaire, S. M. Prescott, G. A. Zimmerman, et al. Oxidized Alkyl Phospholipids Are Specific, High Affinity Peroxisome Proliferator-activated Receptor gamma Ligands and Agonists J. Biol. Chem., May 4, 2001; 276(19): 16015 - 16023. [Abstract] [Full Text] [PDF]