Oxidation of low density lipoprotein (LDL) may be involved in the development of atherosclerosis. It has recently been shown that -tocopherol (-TOH) can act either as an antioxidant or prooxidant for isolated low density lipoprotein (LDL). In the absence of an effective co-antioxidant, -TOH is a prooxidant and this activity is evidently due to reaction of the -tocopheroxyl radical (-TO) with the LDL's polyunsaturated lipids (Bowry, V. B., and Stocker, R.(1993) J. Am. Chem. Soc. 115, 6029-6045). Herein we examined the effectiveness of selected natural and synthetic radical scavengers as co-antioxidants for inhibiting peroxyl radical-induced peroxidation in LDL that is devoid of ubiquinol-10 (an effective endogenous co-antioxidant) but still contains most of its natural complement of -TOH. Various quinols, catechols, and aminophenols, as well as ascorbate, 6-palmityl ascorbate, and bilirubin, were very effective co-antioxidants under our test conditions, whereas ordinary phenolic antioxidants, including short-tailed -TOH homologues, were less effective. Reduced glutathione, urate, and Probucol were ineffective. These findings confirm that the prooxidant activity of -TOH in LDL relies heavily on the segregation of water-insoluble radicals (particularly -TO) into individual LDL particles, since it was those compounds that are expected to either irreversibly reduce -TO or accelerate the diffusion of radicals between particles which most effectively inhibited the tocopherol-mediated phase of peroxidation. Theoretical and practical implications of these findings are discussed, as is their relevance to the ``LDL oxidation'' hypothesis of atherogenesis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				J. L. Gardner, S. M. Turner, A. Bautista, G. Lindwall, M. Awada, and M. K. Hellerstein Measurement of liver collagen synthesis by heavy water labeling: effects of profibrotic toxicants and antifibrotic interventions Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1695 - G1705. [Abstract] [Full Text] [PDF]

				S. Mishra, T. Fujita, V. N. Lama, D. Nam, H. Liao, M. Okada, K. Minamoto, Y. Yoshikawa, H. Harada, and D. J. Pinsky Carbon monoxide rescues ischemic lungs by interrupting MAPK-driven expression of early growth response 1 gene and its downstream target genes PNAS, March 28, 2006; 103(13): 5191 - 5196. [Abstract] [Full Text] [PDF]

				S. Delanian, R. Porcher, J. Rudant, and J.-L. Lefaix Kinetics of Response to Long-Term Treatment Combining Pentoxifylline and Tocopherol in Patients With Superficial Radiation-Induced Fibrosis J. Clin. Oncol., December 1, 2005; 23(34): 8570 - 8579. [Abstract] [Full Text] [PDF]

				E. R. Miller III, R. Pastor-Barriuso, D. Dalal, R. A. Riemersma, L. J. Appel, and E. Guallar Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality Ann Intern Med, January 4, 2005; 142(1): 37 - 46. [Abstract] [Full Text] [PDF]

				R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]

				Y. Homma, Y. Kondo, M. Kaneko, T. Kitamura, W. T. Nyou, M. Yanagisawa, Y. Yamamoto, and T. Kakizoe Promotion of carcinogenesis and oxidative stress by dietary cholesterol in rat prostate Carcinogenesis, June 1, 2004; 25(6): 1011 - 1014. [Abstract] [Full Text] [PDF]

				R. Stocker and R. A O'Halloran Dealcoholized red wine decreases atherosclerosis in apolipoprotein E gene-deficient mice independently of inhibition of lipid peroxidation in the artery wall Am. J. Clinical Nutrition, January 1, 2004; 79(1): 123 - 130. [Abstract] [Full Text] [PDF]

				O. Ogawa, X. Zhu, G. Perry, and M. A. Smith Mitochondrial Abnormalities and Oxidative Imbalance in Neurodegenerative Disease Sci. Aging Knowl. Environ., October 16, 2002; 2002(41): pe16 - 16. [Abstract] [Full Text]

				A. C. Terentis, S. R. Thomas, J. A. Burr, D. C. Liebler, and R. Stocker Vitamin E Oxidation in Human Atherosclerotic Lesions Circ. Res., February 22, 2002; 90(3): 333 - 339. [Abstract] [Full Text] [PDF]

				D. Heydeck, J. M. Upston, H. Viita, S. Yla-Herttuala, and R. Stocker Oxidation of LDL by rabbit and human 15-lipoxygenase: prevalence of nonenzymatic reactions J. Lipid Res., July 1, 2001; 42(7): 1082 - 1088. [Abstract] [Full Text] [PDF]

				W. W. Poon, D. E. Davis, H. T. Ha, T. Jonassen, P. N. Rather, and C. F. Clarke Identification of Escherichia coli ubiB, a Gene Required for the First Monooxygenase Step in Ubiquinone Biosynthesis J. Bacteriol., September 15, 2000; 182(18): 5139 - 5146. [Abstract] [Full Text]

				E. Porkkala-Sarataho, J. T. Salonen, K. Nyyssonen, J. Kaikkonen, R. Salonen, U. Ristonmaa, U. Diczfalusy, R. Brigelius-Flohe, S. Loft, and H. E. Poulsen Long-Term Effects of Vitamin E, Vitamin C, and Combined Supplementation on Urinary 7-Hydro-8-Oxo-2'-Deoxyguanosine, Serum Cholesterol Oxidation Products, and Oxidation Resistance of Lipids in Nondepleted Men Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2087 - 2093. [Abstract] [Full Text] [PDF]

				T. Jonassen and C. F. Clarke Isolation and Functional Expression of Human COQ3, a Gene Encoding a Methyltransferase Required for Ubiquinone Biosynthesis J. Biol. Chem., April 21, 2000; 275(17): 12381 - 12387. [Abstract] [Full Text] [PDF]

				W. W. Poon, R. J. Barkovich, A. Y. Hsu, A. Frankel, P. T. Lee, J. N. Shepherd, D. C. Myles, and C. F. Clarke Yeast and Rat Coq3 and Escherichia coli UbiG Polypeptides Catalyze Both O-Methyltransferase Steps in Coenzyme Q Biosynthesis J. Biol. Chem., July 30, 1999; 274(31): 21665 - 21672. [Abstract] [Full Text] [PDF]

				A. C Carr and B. Frei Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans Am. J. Clinical Nutrition, June 1, 1999; 69(6): 1086 - 1107. [Abstract] [Full Text] [PDF]

				J. M. UPSTON, A. C. TERENTIS, and R. STOCKER Tocopherol-mediated peroxidation of lipoproteins: implications for vitamin E as a potential antiatherogenic supplement FASEB J, June 1, 1999; 13(9): 977 - 994. [Abstract] [Full Text]

				A. CARR and B. FREI Does vitamin C act as a pro-oxidant under physiological conditions? FASEB J, June 1, 1999; 13(9): 1007 - 1024. [Abstract] [Full Text]

				P. K. WITTING, K. PETTERSSON, A.-M. ÖSTLUND-LINDQVIST, C. WESTERLUND, A. W. ERIKSSON, and R. STOCKER Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice FASEB J, April 1, 1999; 13(6): 667 - 675. [Abstract] [Full Text]

				J. Belkner, H. Stender, and H. Kuhn The Rabbit 15-Lipoxygenase Preferentially Oxygenates LDL Cholesterol Esters, and This Reaction Does Not Require Vitamin E J. Biol. Chem., September 4, 1998; 273(36): 23225 - 23232. [Abstract] [Full Text] [PDF]

				B. Garner, P. K. Witting, A. R. Waldeck, J. K. Christison, M. Raftery, and R. Stocker Oxidation of High Density Lipoproteins. I. FORMATION OF METHIONINE SULFOXIDE IN APOLIPOPROTEINS AI AND AII IS AN EARLY EVENT THAT ACCOMPANIES LIPID PEROXIDATION AND CAN BE ENHANCED BY alpha -TOCOPHEROL J. Biol. Chem., March 13, 1998; 273(11): 6080 - 6087. [Abstract] [Full Text] [PDF]

				J. Neuzil, J. K. Christison, E. Iheanacho, J.-C. Fragonas, V. Zammit, N. H. Hunt, and R. Stocker Radical-induced lipoprotein and plasma lipid oxidation in normal and apolipoprotein E gene knockout (apoE-/-) mice: apoE-/- mouse as a model for testing the role of tocopherol-mediated peroxidation in atherogenesis J. Lipid Res., February 1, 1998; 39(2): 354 - 368. [Abstract] [Full Text]

				J. M. Upston, P. K. Witting, R. Alleva, and R. Stocker Oxidation of Free Fatty Acids in Low Density Lipoprotein by 15-Lipoxygenase Stimulates Nonenzymic, alpha -Tocopherol-mediated Peroxidation of Cholesteryl Esters J. Biol. Chem., November 28, 1997; 272(48): 30067 - 30074. [Abstract] [Full Text] [PDF]

				J. Neuzil, P. K. Witting, and R. Stocker alpha -Tocopheryl hydroquinone is an efficient multifunctional inhibitor of radical-initiated oxidation of low density lipoprotein lipids PNAS, July 22, 1997; 94(15): 7885 - 7890. [Abstract] [Full Text] [PDF]

				S. R. Thomas, P. K. Witting, and R. Stocker 3-Hydroxyanthranilic Acid Is an Efficient, Cell-derived Co-antioxidant for alpha -Tocopherol, Inhibiting Human Low Density Lipoprotein and Plasma Lipid Peroxidation J. Biol. Chem., December 20, 1996; 271(51): 32714 - 32721. [Abstract] [Full Text] [PDF]

				S. R. Thomas, J. Neuzil, and R. Stocker Cosupplementation With Coenzyme Q Prevents the Prooxidant Effect of {alpha}-Tocopherol and Increases the Resistance of LDL to Transition Metal–Dependent Oxidation Initiation Arterioscler. Thromb. Vasc. Biol., May 1, 1996; 16(5): 687 - 696. [Abstract] [Full Text]

				B. N. Marbois and C. F. Clarke The COQ7 Gene Encodes a Protein in Saccharomyces cerevisiae Necessary for Ubiquinone Biosynthesis J. Biol. Chem., February 9, 1996; 271(6): 2995 - 3004. [Abstract] [Full Text] [PDF]

				A. C. Terentis, S. R. Thomas, J. A. Burr, D. C. Liebler, and R. Stocker Vitamin E Oxidation in Human Atherosclerotic Lesions Circ. Res., February 22, 2002; 90(3): 333 - 339. [Abstract] [Full Text] [PDF]